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PROFESSOR: OK, OK.

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00:00:23,790 --> 00:00:27,150
The weekend is over.

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00:00:27,150 --> 00:00:28,400
One announcement.

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00:00:30,700 --> 00:00:34,130
Last weekly test will be
tomorrow, and it'll be based

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00:00:34,130 --> 00:00:37,690
on homework 11, focused
on polymers.

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00:00:37,690 --> 00:00:41,900
And then the following week
is the very last week of

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00:00:41,900 --> 00:00:45,780
semester, and there's no
testing, no work required of

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00:00:45,780 --> 00:00:48,350
you, when the subject
has a final exam.

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00:00:48,350 --> 00:00:50,860
And this one has a big final
exam, big celebration, so

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00:00:50,860 --> 00:00:52,620
there will be no weekly
test next Tuesday.

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00:00:52,620 --> 00:00:56,890
So this is the last one,
so get out the Kleenex.

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00:00:56,890 --> 00:00:57,220
All right.

20
00:00:57,220 --> 00:01:01,300
So today we want to continue the
treatment of biochemistry.

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00:01:01,300 --> 00:01:04,300
Last day we started looking at
proteins, and the building

22
00:01:04,300 --> 00:01:06,530
blocks of proteins
are amino acids.

23
00:01:06,530 --> 00:01:10,370
And so we looked at the basic
structure of amino acids,

24
00:01:10,370 --> 00:01:14,530
shown here, which is an sp3
hybridized central carbon,

25
00:01:14,530 --> 00:01:16,800
which I've designated
alpha carbon.

26
00:01:16,800 --> 00:01:20,290
And three of the four
bonds are the same

27
00:01:20,290 --> 00:01:21,440
in every amino acid.

28
00:01:21,440 --> 00:01:23,700
Every amino acid has,
off the central

29
00:01:23,700 --> 00:01:25,250
carbon, an amino group.

30
00:01:25,250 --> 00:01:27,560
This is the nitrogen
with two hydrogens.

31
00:01:27,560 --> 00:01:30,290
It has a hydrogen, a lone
hydrogen, and it has a

32
00:01:30,290 --> 00:01:33,620
carboxylic acid, which
is this COOH.

33
00:01:33,620 --> 00:01:36,560
Double bond here, I'm looking at
four sticks off the carbon.

34
00:01:36,560 --> 00:01:38,100
One, two, three, four.

35
00:01:38,100 --> 00:01:43,300
And this proton here is the one
that can fall off and go

36
00:01:43,300 --> 00:01:44,320
over to the side.

37
00:01:44,320 --> 00:01:47,200
And when it does so, then
we end up with the acid.

38
00:01:47,200 --> 00:01:48,470
It's a proton donor.

39
00:01:48,470 --> 00:01:52,260
And then the fourth bond
is this designated R.

40
00:01:52,260 --> 00:01:55,790
R is the substituent, and
it could be anything.

41
00:01:55,790 --> 00:01:57,650
We could put a cyanide
up there, if we want.

42
00:01:57,650 --> 00:02:02,810
Anything that conforms to this
architecture with whatever

43
00:02:02,810 --> 00:02:05,390
choice of R is still qualified
as amino acid.

44
00:02:05,390 --> 00:02:07,660
There are only twenty
choices of R that

45
00:02:07,660 --> 00:02:09,620
are found in protein.

46
00:02:09,620 --> 00:02:12,040
We also studied chirality,
which is handedness.

47
00:02:12,040 --> 00:02:16,360
Some of these amino acid
molecules are chiral.

48
00:02:16,360 --> 00:02:20,720
That is to say, if you put this
carboxylic acid in the

49
00:02:20,720 --> 00:02:23,970
lower left, and the amino group
in the lower right, you

50
00:02:23,970 --> 00:02:27,110
have molecules that are
seemingly identical, but not

51
00:02:27,110 --> 00:02:28,100
superimposable.

52
00:02:28,100 --> 00:02:29,520
We call them chiral.

53
00:02:29,520 --> 00:02:32,900
And the two forms are
called enantiomers.

54
00:02:32,900 --> 00:02:36,020
And only the L-enantiomer
is found in proteins.

55
00:02:36,020 --> 00:02:38,370
And we saw that the L is
determined on the basis of

56
00:02:38,370 --> 00:02:42,270
polarization rotation
of light in an

57
00:02:42,270 --> 00:02:44,040
aqueous solution of this.

58
00:02:44,040 --> 00:02:45,120
Except for lycene.

59
00:02:45,120 --> 00:02:47,280
In the case of lycene,
we have H up here.

60
00:02:47,280 --> 00:02:48,880
So we have an H above
and an H below.

61
00:02:48,880 --> 00:02:50,610
That molecule is not chiral.

62
00:02:50,610 --> 00:02:53,310
So nineteen of the twenty amino
acids that we find in

63
00:02:53,310 --> 00:02:55,960
proteins exhibit chirality.

64
00:02:55,960 --> 00:02:59,500
And later in the lecture we
started looking at aqueous

65
00:02:59,500 --> 00:03:03,380
solution behavior of
the amino acids.

66
00:03:03,380 --> 00:03:07,070
And what happens is, when they
dissolve in aqueous solution,

67
00:03:07,070 --> 00:03:08,780
they form zwitterions.

68
00:03:08,780 --> 00:03:11,030
Zwitterions by proton
transfer.

69
00:03:11,030 --> 00:03:15,680
So the proton goes off the
carboxylic acid and joins the

70
00:03:15,680 --> 00:03:18,920
amino end, so you have a plus
end and a minus end.

71
00:03:18,920 --> 00:03:22,880
And then we looked at what
happens with the behavior in

72
00:03:22,880 --> 00:03:25,760
aqueous solution, and
we came up with the

73
00:03:25,760 --> 00:03:27,430
Henderson-Hasselbalch
equation.

74
00:03:27,430 --> 00:03:28,770
And here it is, plotted.

75
00:03:28,770 --> 00:03:30,470
This is the case for alanine.

76
00:03:30,470 --> 00:03:32,730
In the case of alanine, we have
the methyl group here.

77
00:03:32,730 --> 00:03:34,830
So the R is CH3.

78
00:03:34,830 --> 00:03:35,950
Everything else is the same.

79
00:03:35,950 --> 00:03:39,100
So you can see that here's the
neutral zwitterion, where the

80
00:03:39,100 --> 00:03:43,410
H off of the carboxylic acid,
has transferred over

81
00:03:43,410 --> 00:03:44,710
to the amino end.

82
00:03:44,710 --> 00:03:46,230
We have charge neutrality.

83
00:03:46,230 --> 00:03:49,810
The molecule started off net
neutral, and now the plus is

84
00:03:49,810 --> 00:03:52,850
over here, conferring a positive
charge to this end,

85
00:03:52,850 --> 00:03:56,070
and leaving this end less
a positive charge,

86
00:03:56,070 --> 00:03:57,130
and therefore minus.

87
00:03:57,130 --> 00:04:01,770
So it's globally neutral, but
locally positive and negative.

88
00:04:01,770 --> 00:04:04,330
Hence the term zwitterion,
because it's essentially dual

89
00:04:04,330 --> 00:04:06,730
gender, both positive
and negative.

90
00:04:06,730 --> 00:04:10,050
And we looked at the aqueous
solution behavior of the

91
00:04:10,050 --> 00:04:13,590
zwitterion, and we saw that
zwitterion is responsive to

92
00:04:13,590 --> 00:04:14,170
its environment.

93
00:04:14,170 --> 00:04:17,390
And we reasoned that this is
how you start to impart

94
00:04:17,390 --> 00:04:19,180
animation to something.

95
00:04:19,180 --> 00:04:20,530
How do you get something
animated?

96
00:04:20,530 --> 00:04:23,250
You get something animated by
having it respond to its

97
00:04:23,250 --> 00:04:24,060
environment.

98
00:04:24,060 --> 00:04:25,060
A rock sits there.

99
00:04:25,060 --> 00:04:28,060
You can talk to the rock,
nothing happens to the rock.

100
00:04:28,060 --> 00:04:30,960
But animated objects, if they're
endowed with hearing,

101
00:04:30,960 --> 00:04:32,880
if you talk to them, sometimes
they respond.

102
00:04:32,880 --> 00:04:34,000
So what's going on there?

103
00:04:34,000 --> 00:04:38,090
It to do with the ability
to respond chemically.

104
00:04:38,090 --> 00:04:40,130
And so what we saw
here is, when we

105
00:04:40,130 --> 00:04:42,560
went into low pH regime--

106
00:04:42,560 --> 00:04:46,350
low pH means very, very high
proton concentration.

107
00:04:46,350 --> 00:04:49,800
The zwitterion responds by the
le Chatelier principle to try

108
00:04:49,800 --> 00:04:52,190
to minimize that acidity.

109
00:04:52,190 --> 00:04:53,870
So it gobbles up protons.

110
00:04:53,870 --> 00:04:57,160
And over here we see that
it gobbles up protons by

111
00:04:57,160 --> 00:05:00,060
attaching to this carboxylic
acid end.

112
00:05:00,060 --> 00:05:01,670
That's a proton attachment
site.

113
00:05:01,670 --> 00:05:06,490
And in the extreme, all of the
zwitterions have been capped

114
00:05:06,490 --> 00:05:07,340
by protons.

115
00:05:07,340 --> 00:05:11,750
So over here we have complete
protonation, and that's what

116
00:05:11,750 --> 00:05:15,810
we're showing in this graph
here, which is just basically

117
00:05:15,810 --> 00:05:18,370
the one that's up on the
screen, but I'm using

118
00:05:18,370 --> 00:05:19,720
different-- see, this
is taken from one

119
00:05:19,720 --> 00:05:21,200
of the biology readings.

120
00:05:21,200 --> 00:05:23,080
They say equivalence
of hydroxyl.

121
00:05:23,080 --> 00:05:24,490
There's no hydroxyl here.

122
00:05:24,490 --> 00:05:25,210
I don't know how these--

123
00:05:25,210 --> 00:05:28,280
you know, the language of some
of these branches of

124
00:05:28,280 --> 00:05:29,700
science puzzle me.

125
00:05:29,700 --> 00:05:31,660
That's equivalence
of hydroxyl, but

126
00:05:31,660 --> 00:05:32,900
we don't have hydroxyl!

127
00:05:32,900 --> 00:05:34,660
It's all about protons.

128
00:05:34,660 --> 00:05:38,830
So here it is, in terms of the
equivalence of H plus.

129
00:05:38,830 --> 00:05:40,370
So here's the neutral
zwitterion.

130
00:05:40,370 --> 00:05:42,000
That's this thing here.

131
00:05:42,000 --> 00:05:46,810
And this H, if it falls off, it
can then become the neutral

132
00:05:46,810 --> 00:05:47,410
zwitterion.

133
00:05:47,410 --> 00:05:53,740
And then what happens is, as
we go to very, very low pH,

134
00:05:53,740 --> 00:05:55,420
what happens is that
the zwitterion

135
00:05:55,420 --> 00:05:56,920
starts attaching protons.

136
00:05:56,920 --> 00:05:59,270
So this is a neutral zwitterion
to which we've

137
00:05:59,270 --> 00:06:00,240
attached the H.

138
00:06:00,240 --> 00:06:01,040
So it's much--

139
00:06:01,040 --> 00:06:02,680
to me this is transparent.

140
00:06:02,680 --> 00:06:04,230
What this reads--

141
00:06:04,230 --> 00:06:04,710
I don't know.

142
00:06:04,710 --> 00:06:05,770
Equivalence of OH?

143
00:06:05,770 --> 00:06:06,700
There's no OH.

144
00:06:06,700 --> 00:06:08,945
That's a way of saying it's
fully protonated.

145
00:06:08,945 --> 00:06:10,820
BUt to me that's sort
of a backwards way.

146
00:06:10,820 --> 00:06:11,940
Don't tell me what it isn't.

147
00:06:11,940 --> 00:06:13,130
Tell me what it is.

148
00:06:13,130 --> 00:06:15,480
So this is fully protonated
over here.

149
00:06:15,480 --> 00:06:20,240
And as the pH rises, the
zwitterion feels less

150
00:06:20,240 --> 00:06:24,360
compelled to gobble up the
protons, so it sheds protons.

151
00:06:24,360 --> 00:06:27,670
And finally the pH gets to a
point that's high enough that

152
00:06:27,670 --> 00:06:31,900
the zwitterion plays no role,
and it exists as the neutral

153
00:06:31,900 --> 00:06:32,900
zwitterion.

154
00:06:32,900 --> 00:06:36,230
That's the isoelectric point.

155
00:06:36,230 --> 00:06:38,830
We have a 100% concentration
of zwitterion.

156
00:06:38,830 --> 00:06:40,540
Then we go to the
other extreme.

157
00:06:40,540 --> 00:06:43,110
The other extreme is
the high pH regime,

158
00:06:43,110 --> 00:06:45,150
where it's proton deficient.

159
00:06:45,150 --> 00:06:47,220
And so zwitterion
responds by--

160
00:06:47,220 --> 00:06:47,670
what?

161
00:06:47,670 --> 00:06:49,030
Throwing out hydroxyls?

162
00:06:49,030 --> 00:06:49,850
No!

163
00:06:49,850 --> 00:06:52,750
In spite of what's written here,
there are no hydroxyls.

164
00:06:52,750 --> 00:06:57,160
What zwitterion does, is it
tries to shed protons to

165
00:06:57,160 --> 00:06:59,650
compensate for the proton
deficiency.

166
00:06:59,650 --> 00:07:03,320
And so some of the HAs become
just A minus, because the H's

167
00:07:03,320 --> 00:07:04,730
are being liberated.

168
00:07:04,730 --> 00:07:09,700
And over here at the extreme,
all of the zwitterion has lost

169
00:07:09,700 --> 00:07:11,280
its H here.

170
00:07:11,280 --> 00:07:13,990
And so now you have something
that's net negative.

171
00:07:13,990 --> 00:07:15,900
Over here you have something
that's net positive.

172
00:07:15,900 --> 00:07:17,840
In the center it's
net neutral.

173
00:07:17,840 --> 00:07:22,990
So this is the high pH regime,
low pH regime, and this is the

174
00:07:22,990 --> 00:07:25,210
Henderson-Hasselbalch equation,
which answers the

175
00:07:25,210 --> 00:07:30,370
question, what is the ratio of
neutral zwitterion to either

176
00:07:30,370 --> 00:07:33,990
the deprotonated form or
the protonated form as

177
00:07:33,990 --> 00:07:35,830
a function of pH?

178
00:07:35,830 --> 00:07:40,030
You tell me the pH, and I'll
tell you what the ratio is.

179
00:07:40,030 --> 00:07:42,510
Last thing that's really cool
about this, and shows you the

180
00:07:42,510 --> 00:07:47,690
power of this mechanism of
attachment or detachment, is

181
00:07:47,690 --> 00:07:49,110
as follows.

182
00:07:49,110 --> 00:07:49,900
Look at here.

183
00:07:49,900 --> 00:07:54,490
This is not exactly to scale,
but it's reasonable.

184
00:07:54,490 --> 00:07:55,910
You see the pK?

185
00:07:55,910 --> 00:07:57,020
This is pK1.

186
00:07:57,020 --> 00:07:59,770
This is for the protonating
reaction.

187
00:07:59,770 --> 00:08:03,970
So over here I have neutral
zwitterion, over here I have

188
00:08:03,970 --> 00:08:06,650
no neutral zwitterion, all
the zwitterions are fully

189
00:08:06,650 --> 00:08:07,530
protonated.

190
00:08:07,530 --> 00:08:09,260
And in between, I've got--

191
00:08:09,260 --> 00:08:11,390
this is supposed to be sort
of halfway across here.

192
00:08:11,390 --> 00:08:13,300
So this is 50-50.

193
00:08:13,300 --> 00:08:14,200
But look at what happens.

194
00:08:14,200 --> 00:08:26,910
For very, very large changes
in ratio of zwitterion to

195
00:08:26,910 --> 00:08:30,780
protonated zwitterion, the pH
doesn't change that much.

196
00:08:30,780 --> 00:08:34,620
The pH changes a lot here, and
it changes a lot here.

197
00:08:34,620 --> 00:08:38,970
But over a vast expanse of
protonation or deprotonation,

198
00:08:38,970 --> 00:08:42,540
the pH kind of hovers
around pK1.

199
00:08:42,540 --> 00:08:44,800
So the zwitterion is really
doing its job.

200
00:08:44,800 --> 00:08:48,610
It's trying to hold that
solution from shifting pH

201
00:08:48,610 --> 00:08:49,590
dramatically.

202
00:08:49,590 --> 00:08:55,840
We say that zwitterion, by doing
so, acts as a buffer.

203
00:08:55,840 --> 00:09:03,110
A buffer holds pH
near constant.

204
00:09:03,110 --> 00:09:05,420
And the near constant value
it's going to hold

205
00:09:05,420 --> 00:09:07,910
it to is its pK.

206
00:09:07,910 --> 00:09:14,050
So in the acidic regime, in the
very low pH regime, over a

207
00:09:14,050 --> 00:09:17,830
broad range of protonation
deprotonation, it's going to

208
00:09:17,830 --> 00:09:19,210
be roughly a pK1.

209
00:09:19,210 --> 00:09:20,760
And the same thing happens
over here.

210
00:09:20,760 --> 00:09:21,340
You see?

211
00:09:21,340 --> 00:09:26,810
Over a broad range of A minus
to HA, the pH kind of holds

212
00:09:26,810 --> 00:09:27,860
around pK2.

213
00:09:27,860 --> 00:09:30,690
And then finally, over here, the
system gives up and then

214
00:09:30,690 --> 00:09:34,700
it shoots up to the
100% deprotonated.

215
00:09:34,700 --> 00:09:40,310
So that's the story there, and
you see the isoelectric point

216
00:09:40,310 --> 00:09:41,000
in the middle.

217
00:09:41,000 --> 00:09:44,800
Now, so far all we've done is
we've said what happens when

218
00:09:44,800 --> 00:09:52,410
we have a simple amino acid that
has just the one proton

219
00:09:52,410 --> 00:09:55,020
attachment point on the
carboxylic acid

220
00:09:55,020 --> 00:09:56,100
and the amino acid.

221
00:09:56,100 --> 00:09:58,170
But it can get more
complicated.

222
00:09:58,170 --> 00:10:01,730
And there is an example in the
homework that you might want

223
00:10:01,730 --> 00:10:04,700
to look at before
the final exam.

224
00:10:04,700 --> 00:10:09,150
And that's the case where the R
group itself has the ability

225
00:10:09,150 --> 00:10:11,390
to protonate or deprotonate.

226
00:10:11,390 --> 00:10:16,630
Suppose this R group had
a COOH ending here.

227
00:10:16,630 --> 00:10:19,450
Can you see that it could
also participate?

228
00:10:19,450 --> 00:10:22,570
And so then the isoelectric
point isn't simply going to be

229
00:10:22,570 --> 00:10:26,600
the average of the
pK1 and the pK2.

230
00:10:26,600 --> 00:10:29,560
Because now there's a pK for
this thing, as well.

231
00:10:29,560 --> 00:10:33,480
So this is the example
of the tritratable--

232
00:10:33,480 --> 00:10:36,070
that's the term they use.

233
00:10:36,070 --> 00:10:38,950
If I could just spell it, I
could convey the information.

234
00:10:41,820 --> 00:10:43,930
Titratable R group.

235
00:10:43,930 --> 00:10:45,380
That's what they're
talking about.

236
00:10:45,380 --> 00:10:46,960
Otherwise, if the R group is a

237
00:10:46,960 --> 00:10:48,420
neutral, it's just a spectator.

238
00:10:48,420 --> 00:10:50,510
Doesn't doesn't participate
any more than this.

239
00:10:50,510 --> 00:10:51,990
See, here's a hydrogen.

240
00:10:51,990 --> 00:10:53,450
Look at this one, people.

241
00:10:53,450 --> 00:10:54,650
You see this hydrogen?

242
00:10:54,650 --> 00:10:55,860
It doesn't participate at all.

243
00:10:55,860 --> 00:10:58,060
Please don't tell me at some
point that the zwitterion

244
00:10:58,060 --> 00:11:00,200
says, I'm out of hydrogens
from here, I'm out of

245
00:11:00,200 --> 00:11:02,070
hydrogens for here, I'm going
to start shedding this.

246
00:11:02,070 --> 00:11:04,560
This is a really strong
covalent bond.

247
00:11:04,560 --> 00:11:06,495
It's not going anywhere.

248
00:11:06,495 --> 00:11:09,120
If you want titration, you've
got to put the titratable R

249
00:11:09,120 --> 00:11:10,560
group up here.

250
00:11:10,560 --> 00:11:12,440
OK?

251
00:11:12,440 --> 00:11:14,200
This is so cool.

252
00:11:14,200 --> 00:11:16,380
So now, I'm going to show you
an application of this stuff

253
00:11:16,380 --> 00:11:19,540
that's used in biology.

254
00:11:19,540 --> 00:11:22,790
And I know, because one year
they gave a crash course for

255
00:11:22,790 --> 00:11:26,820
engineering faculty in biology,
and we did we

256
00:11:26,820 --> 00:11:29,100
actually did this experiment
in the lab.

257
00:11:29,100 --> 00:11:31,670
So I'm going to show you how
you can use the fact that

258
00:11:31,670 --> 00:11:35,910
zwitterion changes in response
to its environment in the

259
00:11:35,910 --> 00:11:36,490
laboratory.

260
00:11:36,490 --> 00:11:37,950
So what we're going to
do is I'm going to

261
00:11:37,950 --> 00:11:39,820
make a column here.

262
00:11:39,820 --> 00:11:50,460
This is a column, and it's an
aqueous solution, a column of

263
00:11:50,460 --> 00:11:56,120
varying pH.

264
00:11:56,120 --> 00:11:58,590
So it starts at the top, and
just for argument's sake, I'm

265
00:11:58,590 --> 00:12:03,090
going to put high pH here at
the top, and low pH here.

266
00:12:03,090 --> 00:12:04,370
So it's an aqueous solution.

267
00:12:04,370 --> 00:12:05,160
You can say, wait a minute.

268
00:12:05,160 --> 00:12:07,170
He just taught us fixed laws.

269
00:12:07,170 --> 00:12:09,650
This is proton deficient
this is proton rich.

270
00:12:09,650 --> 00:12:12,780
Aren't the protons going to go
north and the hydroxyls are

271
00:12:12,780 --> 00:12:13,830
going to go south?

272
00:12:13,830 --> 00:12:14,600
Yes.

273
00:12:14,600 --> 00:12:15,740
So what are we going to do?

274
00:12:15,740 --> 00:12:19,650
We are going to slow
down diffusion.

275
00:12:19,650 --> 00:12:22,110
We're going to change the
diffusion coefficient, and

276
00:12:22,110 --> 00:12:25,340
what we're going to do is, we're
going to fill this with

277
00:12:25,340 --> 00:12:30,590
a solid suspension and
turn it into a gel.

278
00:12:30,590 --> 00:12:32,190
So what's the function
of the gel?

279
00:12:32,190 --> 00:12:34,570
Don't say that Professor
Sadoway said

280
00:12:34,570 --> 00:12:36,000
that he stopped diffusion.

281
00:12:36,000 --> 00:12:39,420
Diffusion goes on, but it
goes on at a slow rate.

282
00:12:39,420 --> 00:12:42,730
So over the time duration of
the experiment, for all

283
00:12:42,730 --> 00:12:48,100
intents and purposes, the pH
changes imperceptibly in

284
00:12:48,100 --> 00:12:50,260
comparison to everything
else that's going on.

285
00:12:50,260 --> 00:12:51,530
It's all about time scales.

286
00:12:51,530 --> 00:12:54,010
You realize, we are all aging.

287
00:12:54,010 --> 00:12:56,590
We've been aging ever since
I started this lecture.

288
00:12:56,590 --> 00:12:58,440
But for all intents and
purposes, we can view

289
00:12:58,440 --> 00:13:00,770
ourselves as being the
age we were when we

290
00:13:00,770 --> 00:13:02,200
walked in the room.

291
00:13:02,200 --> 00:13:04,435
And even over the semester,
chances are.

292
00:13:04,435 --> 00:13:05,290
All right?

293
00:13:05,290 --> 00:13:08,300
Now if we meet back here in ten
years' time, expect to see

294
00:13:08,300 --> 00:13:09,910
some changes.

295
00:13:09,910 --> 00:13:10,460
Right?

296
00:13:10,460 --> 00:13:13,590
But over the time scale of the
experiment, we can say we take

297
00:13:13,590 --> 00:13:14,720
diffusion out.

298
00:13:14,720 --> 00:13:17,770
So that means the high pH is
here, the low pH is here.

299
00:13:17,770 --> 00:13:20,790
Now what I want to do, what is
it I'm trying to accomplish?

300
00:13:20,790 --> 00:13:27,405
I want to separate an
amino acid mix.

301
00:13:33,590 --> 00:13:35,900
And just for grins and chuckles,
we're going to have

302
00:13:35,900 --> 00:13:38,260
A1, A2, and A3.

303
00:13:38,260 --> 00:13:39,570
Three different amino acids.

304
00:13:39,570 --> 00:13:42,200
Which means just three of
these things, but three

305
00:13:42,200 --> 00:13:44,570
different R values.

306
00:13:44,570 --> 00:13:46,470
I'm going to pour
them the top.

307
00:13:46,470 --> 00:13:48,090
I've got this aqueous
solution, got

308
00:13:48,090 --> 00:13:49,790
all three amino acids.

309
00:13:49,790 --> 00:13:53,850
So what happens when
they fall in here?

310
00:13:53,850 --> 00:13:57,310
When they fall in here, they
start diffusing, too.

311
00:13:57,310 --> 00:13:57,840
Right?

312
00:13:57,840 --> 00:14:01,150
Well, first of all, they hit a
very, very high pH regime.

313
00:14:01,150 --> 00:14:04,500
So what what's the immediate
response to those amino acids

314
00:14:04,500 --> 00:14:06,090
in a high pH regime?

315
00:14:06,090 --> 00:14:07,230
They're all amino acids.

316
00:14:07,230 --> 00:14:08,960
They're all those rescuers.

317
00:14:08,960 --> 00:14:11,420
And they say, Hi, pH.

318
00:14:11,420 --> 00:14:12,450
It's proton deficient?

319
00:14:12,450 --> 00:14:13,050
I can help!

320
00:14:13,050 --> 00:14:14,410
And they all start
shedding protons.

321
00:14:14,410 --> 00:14:17,430
And so within moments,
all of those amino

322
00:14:17,430 --> 00:14:19,040
acids have been totally--

323
00:14:19,040 --> 00:14:20,070
as they say in California--

324
00:14:20,070 --> 00:14:21,810
totally deprotonated.

325
00:14:21,810 --> 00:14:23,140
And here it is.

326
00:14:23,140 --> 00:14:26,210
So they're all sitting there,
in net negative.

327
00:14:26,210 --> 00:14:29,280
They're all sitting there in net
negative, right up here.

328
00:14:29,280 --> 00:14:33,280
But I just told you, I shut off
diffusion, slowed it down.

329
00:14:33,280 --> 00:14:35,460
But I want to get out of
here before dinner.

330
00:14:35,460 --> 00:14:39,450
So I don't want the protons
moving, but I do want the

331
00:14:39,450 --> 00:14:40,870
amino acids to get moving.

332
00:14:40,870 --> 00:14:42,650
So what do I do?

333
00:14:42,650 --> 00:14:45,340
I put on my elecrochemist's
hat, because as you know,

334
00:14:45,340 --> 00:14:47,480
electrochemistry is the highest
form of chemistry, the

335
00:14:47,480 --> 00:14:49,510
most noble form of chemistry.

336
00:14:49,510 --> 00:14:50,800
It happens to be the
area that work in.

337
00:14:50,800 --> 00:14:56,560
And so what we do is we
electrify the ends.

338
00:14:56,560 --> 00:15:00,550
And we'll polarize
the top negative

339
00:15:00,550 --> 00:15:01,790
and the bottom positive.

340
00:15:01,790 --> 00:15:05,230
Well, I just poured in a bunch
of amino acids that became net

341
00:15:05,230 --> 00:15:07,490
negative, and now they're next
to the negative electrode.

342
00:15:07,490 --> 00:15:08,650
So what happens?

343
00:15:08,650 --> 00:15:12,660
Now they're in an electric
field, and they start moving.

344
00:15:12,660 --> 00:15:14,950
They start moving in the
electric field, and they're

345
00:15:14,950 --> 00:15:16,370
all net negative.

346
00:15:16,370 --> 00:15:18,240
But what happens, is they
move down here.

347
00:15:18,240 --> 00:15:21,290
So this is medium pH.

348
00:15:21,290 --> 00:15:21,760
Can you see?

349
00:15:21,760 --> 00:15:23,620
I've established the
pH gradient.

350
00:15:23,620 --> 00:15:28,650
And as they move from high pH
to medium pH, the proton

351
00:15:28,650 --> 00:15:31,040
deficiency isn't as intense.

352
00:15:31,040 --> 00:15:33,220
So they're responding to
their environments.

353
00:15:33,220 --> 00:15:37,080
They're saying, you know, back
there I had to get rid of all

354
00:15:37,080 --> 00:15:37,890
my protons.

355
00:15:37,890 --> 00:15:41,670
But now, it doesn't feel so
proton deficient, so I can

356
00:15:41,670 --> 00:15:44,520
start taking protons on.

357
00:15:44,520 --> 00:15:46,040
They respond to their
environments.

358
00:15:46,040 --> 00:15:48,710
So here, they're
all A minuses.

359
00:15:48,710 --> 00:15:50,270
And if they ever get down here,

360
00:15:50,270 --> 00:15:52,570
they'll all be HAA pluses.

361
00:15:52,570 --> 00:15:54,390
And so what are they in here?

362
00:15:54,390 --> 00:15:56,850
They're sort of on their
way to becoming HAs.

363
00:15:59,520 --> 00:16:03,900
Because the pH is continuously
variable.

364
00:16:03,900 --> 00:16:07,050
So as they become less negative,
what happens to the

365
00:16:07,050 --> 00:16:09,820
driving force by the
negative electrode?

366
00:16:09,820 --> 00:16:10,880
It's weaker.

367
00:16:10,880 --> 00:16:13,800
So the protons were, first
of all, they're anions.

368
00:16:13,800 --> 00:16:14,650
They're net anions.

369
00:16:14,650 --> 00:16:15,420
They go, whoa!

370
00:16:15,420 --> 00:16:15,775
Negative!

371
00:16:15,775 --> 00:16:18,370
And they start moving, and then
they get less and less

372
00:16:18,370 --> 00:16:20,900
negative, and the field gets
weaker and weaker.

373
00:16:20,900 --> 00:16:24,340
And eventually, they take on
enough protons that they

374
00:16:24,340 --> 00:16:26,330
become neutral zwitterions.

375
00:16:26,330 --> 00:16:30,030
And what is the response
of a neutral ion

376
00:16:30,030 --> 00:16:32,400
in an electric field?

377
00:16:32,400 --> 00:16:33,070
Nothing.

378
00:16:33,070 --> 00:16:34,060
It stops.

379
00:16:34,060 --> 00:16:48,520
And so let's say, this happens
to be the isoelectric point of

380
00:16:48,520 --> 00:16:50,280
amino acid number 1.

381
00:16:50,280 --> 00:16:52,470
So it gets to the isoelectric
point, and it

382
00:16:52,470 --> 00:16:53,370
doesn't move anymore.

383
00:16:53,370 --> 00:16:57,040
And number 2 and number 3 keep
going, and this might be the

384
00:16:57,040 --> 00:17:01,580
PI of have number 2, and this
might be the PI of number 3.

385
00:17:01,580 --> 00:17:06,150
And now I want only amino acid
number 1 from this mix, I can

386
00:17:06,150 --> 00:17:08,640
now go in-- this is a gel.

387
00:17:08,640 --> 00:17:10,630
It's put down on the
glass plate, or you

388
00:17:10,630 --> 00:17:11,750
can put it in a column.

389
00:17:11,750 --> 00:17:13,070
Now you where they are.

390
00:17:13,070 --> 00:17:14,030
You come in--

391
00:17:14,030 --> 00:17:15,980
because you've got a pH meter,
you know where this is.

392
00:17:15,980 --> 00:17:16,890
You know the PI.

393
00:17:16,890 --> 00:17:17,270
Bingo.

394
00:17:17,270 --> 00:17:18,480
That's where they are.

395
00:17:18,480 --> 00:17:20,440
And if I want number 2,
they're right here.

396
00:17:20,440 --> 00:17:23,360
And number 3, they're
right here.

397
00:17:23,360 --> 00:17:28,734
So this process is called
gel electrophoresis.

398
00:17:33,590 --> 00:17:35,460
This is the term.

399
00:17:35,460 --> 00:17:37,570
It tells you nothing
about the process.

400
00:17:37,570 --> 00:17:38,960
It tells you how
to conduct it.

401
00:17:38,960 --> 00:17:41,180
You make a gel, and you
polarize the ends.

402
00:17:41,180 --> 00:17:44,150
Electrophoresis is simply
particles moving in an

403
00:17:44,150 --> 00:17:44,800
electric field.

404
00:17:44,800 --> 00:17:47,470
You can paint a car this way.

405
00:17:47,470 --> 00:17:49,900
Obviously the car, when the
car is made of metal.

406
00:17:49,900 --> 00:17:53,080
If you have a fiberglass body,
you can't use electrophoresis.

407
00:17:53,080 --> 00:17:56,840
The car is made of metal, you
polarize the car, and the

408
00:17:56,840 --> 00:17:59,910
paint, the paint has
got dipoles.

409
00:17:59,910 --> 00:18:02,030
And so the paint sticks
to the car.

410
00:18:02,030 --> 00:18:04,010
And then you lift it out, let it
drip, and then just get the

411
00:18:04,010 --> 00:18:06,610
right amount of paint
proportional to the charge you

412
00:18:06,610 --> 00:18:08,470
put on the car by
electrophoresis.

413
00:18:08,470 --> 00:18:10,320
What's that got to
do with this?

414
00:18:10,320 --> 00:18:13,900
It doesn't talk about
the focusing here.

415
00:18:13,900 --> 00:18:20,860
So the mechanism here is called
isoelectric focusing.

416
00:18:20,860 --> 00:18:24,880
So isoelectric focusing is the
principle by which we can

417
00:18:24,880 --> 00:18:28,670
separate the amino acids
from one another.

418
00:18:28,670 --> 00:18:32,160
The gel electrophoresis column
is a device in which we do so.

419
00:18:32,160 --> 00:18:35,110
And let's be modern, so we'll
give it a three-letter

420
00:18:35,110 --> 00:18:36,100
initialization.

421
00:18:36,100 --> 00:18:40,250
IEF, isoelectric focusing.

422
00:18:40,250 --> 00:18:41,950
Isn't that cool?

423
00:18:41,950 --> 00:18:43,410
Yeah.

424
00:18:43,410 --> 00:18:44,210
I thought so.

425
00:18:44,210 --> 00:18:45,020
Anyway.

426
00:18:45,020 --> 00:18:46,090
OK.

427
00:18:46,090 --> 00:18:50,360
Everybody's still zoned out
from turkey or something.

428
00:18:50,360 --> 00:18:52,910
No response.

429
00:18:52,910 --> 00:18:53,660
This is brilliant.

430
00:18:53,660 --> 00:18:55,380
It's beautiful, and it
integrates all of this

431
00:18:55,380 --> 00:18:57,540
material, and deadpan.

432
00:18:57,540 --> 00:18:59,110
All of this withholding love.

433
00:18:59,110 --> 00:19:02,310
You've been with your families,
I can tell.

434
00:19:02,310 --> 00:19:04,800
All of the old family
dynamic, see?

435
00:19:04,800 --> 00:19:05,200
It's here.

436
00:19:05,200 --> 00:19:06,440
You brought it with you.

437
00:19:06,440 --> 00:19:07,090
Leave it!

438
00:19:07,090 --> 00:19:08,250
Leave it at the airport.

439
00:19:08,250 --> 00:19:09,020
OK.

440
00:19:09,020 --> 00:19:09,600
Now.

441
00:19:09,600 --> 00:19:12,530
So we've been talking about
the amino acids.

442
00:19:12,530 --> 00:19:13,960
We said we're going
to use these as

443
00:19:13,960 --> 00:19:15,870
building blocks for proteins.

444
00:19:15,870 --> 00:19:17,900
Let's build some proteins now.

445
00:19:17,900 --> 00:19:19,150
So protein synthesis.

446
00:19:24,630 --> 00:19:28,020
So we're going to make
macromolecule.

447
00:19:28,020 --> 00:19:28,950
What are we making?

448
00:19:28,950 --> 00:19:31,160
We're making a macromolecule.

449
00:19:31,160 --> 00:19:32,410
Protein is a macromolecule.

450
00:19:32,410 --> 00:19:35,240
You notice I didn't say polymer,
because a polymer

451
00:19:35,240 --> 00:19:36,150
going to have--

452
00:19:36,150 --> 00:19:38,550
every element along
the backbone is

453
00:19:38,550 --> 00:19:39,300
going to be the same.

454
00:19:39,300 --> 00:19:42,620
But I'm telling you that we can
change the choice of R at

455
00:19:42,620 --> 00:19:45,270
every station.

456
00:19:45,270 --> 00:19:46,630
So it's a macromolecule,
but it's not

457
00:19:46,630 --> 00:19:47,650
necessarily a polymer.

458
00:19:47,650 --> 00:19:49,570
But we do know, if we're going
back a macromolecule, we've

459
00:19:49,570 --> 00:19:50,540
got two choices.

460
00:19:50,540 --> 00:19:53,050
Addition or condensation
polymerization.

461
00:19:53,050 --> 00:19:55,940
So I look at the basic
structure--

462
00:19:55,940 --> 00:19:59,000
let's put it back the way we
found it, so that people don't

463
00:19:59,000 --> 00:20:03,190
leave thinking that we have
two carboxylic acids.

464
00:20:03,190 --> 00:20:07,480
So the most the most general
form doesn't have a titratable

465
00:20:07,480 --> 00:20:10,700
R group, but it does
have an R up here.

466
00:20:10,700 --> 00:20:14,820
So I want to take one of these
and link it to another one.

467
00:20:14,820 --> 00:20:15,730
So how do I do it?

468
00:20:15,730 --> 00:20:17,410
Well, right off the
bat, addition

469
00:20:17,410 --> 00:20:18,660
polymerization is no good.

470
00:20:18,660 --> 00:20:24,040
Because even if I had enough
energy in my body to form a

471
00:20:24,040 --> 00:20:25,880
radical, what could
I do with this?

472
00:20:25,880 --> 00:20:27,440
There are no double
bonds here!

473
00:20:27,440 --> 00:20:28,580
There are no double
bonds here.

474
00:20:28,580 --> 00:20:32,060
I can't break a double bond and
then allow this to bond to

475
00:20:32,060 --> 00:20:32,920
its neighbor.

476
00:20:32,920 --> 00:20:36,650
So axiomatically, I have
to go with condensation

477
00:20:36,650 --> 00:20:38,050
polymerization.

478
00:20:38,050 --> 00:20:38,910
OK?

479
00:20:38,910 --> 00:20:47,130
Macromolecule formation by
condensation reaction.

480
00:20:47,130 --> 00:20:49,500
I don't even want to say the
word polymerization.

481
00:20:49,500 --> 00:20:53,830
By condensation reaction.

482
00:20:53,830 --> 00:20:53,980
OK.

483
00:20:53,980 --> 00:20:56,290
So let's look at an
example here.

484
00:20:56,290 --> 00:20:58,110
An example will be this.

485
00:20:58,110 --> 00:21:02,400
I'm going to write,
here is the COO R.

486
00:21:02,400 --> 00:21:07,060
So I'm going to show this,
and then over here--

487
00:21:07,060 --> 00:21:10,120
well, maybe I'd better show
some fine structure.

488
00:21:10,120 --> 00:21:11,640
I'll give you a little
more fine structure.

489
00:21:11,640 --> 00:21:17,090
So we'll put the double
bond up here, O minus.

490
00:21:17,090 --> 00:21:21,350
And then over here, I'm
going to put H3N plus.

491
00:21:21,350 --> 00:21:23,440
So here's the neutral
zwitterion, agreed?

492
00:21:23,440 --> 00:21:25,780
And I've got some kind of
an R group up here.

493
00:21:25,780 --> 00:21:29,840
And I'm going to put next to
it a second one of these.

494
00:21:29,840 --> 00:21:35,270
So here's the alpha carbon,
and we'll go COO.

495
00:21:35,270 --> 00:21:38,610
And then over here, I'm going
to unpack this nitrogen.

496
00:21:38,610 --> 00:21:42,870
It's got one, two,
three hydrogens,

497
00:21:42,870 --> 00:21:43,980
and it's net positive.

498
00:21:43,980 --> 00:21:45,060
So there's the neutral
zwitterion.

499
00:21:45,060 --> 00:21:52,170
So now by condensation reaction,
what we'll do is

500
00:21:52,170 --> 00:21:56,320
we'll take this oxygen off of
the left amino acid, and we'll

501
00:21:56,320 --> 00:22:02,920
take two of the hydrogens off
of this amino acid, and we

502
00:22:02,920 --> 00:22:07,450
will eject a water molecule.

503
00:22:07,450 --> 00:22:09,330
We'll eject the water
molecule.

504
00:22:09,330 --> 00:22:10,590
And that's safe.

505
00:22:10,590 --> 00:22:13,880
It's compatible with the body.

506
00:22:13,880 --> 00:22:14,980
And now what's left?

507
00:22:14,980 --> 00:22:16,830
This carbon is naked.

508
00:22:16,830 --> 00:22:18,040
One, two, three.

509
00:22:18,040 --> 00:22:21,700
There's a bond sitting here that
used to go to the oxygen.

510
00:22:21,700 --> 00:22:25,720
And this nitrogen, it's
sitting naked too.

511
00:22:25,720 --> 00:22:29,120
And so now we can do, is we can
make a link between this

512
00:22:29,120 --> 00:22:32,170
carbon and this nitrogen.

513
00:22:32,170 --> 00:22:37,210
And this bond is called
the peptide bond.

514
00:22:37,210 --> 00:22:39,570
This is the peptide bond.

515
00:22:39,570 --> 00:22:40,750
OK?

516
00:22:40,750 --> 00:22:45,910
And we see that the atomic mass
of the dipeptide is less

517
00:22:45,910 --> 00:22:49,990
than the sum of the masses of
the individual components,

518
00:22:49,990 --> 00:22:51,753
because we've lost the water.

519
00:22:55,270 --> 00:22:59,980
So I think I've got
some slides here.

520
00:22:59,980 --> 00:23:01,880
What's here?

521
00:23:01,880 --> 00:23:02,060
Oh.

522
00:23:02,060 --> 00:23:06,160
This is just the various,
pK1 and pK2.

523
00:23:06,160 --> 00:23:09,970
And then this side chain here,
this is the value of the pK

524
00:23:09,970 --> 00:23:11,900
should you have a titratable
R group.

525
00:23:11,900 --> 00:23:13,940
That's why there's the
third column here.

526
00:23:13,940 --> 00:23:14,980
So when you see this--

527
00:23:14,980 --> 00:23:18,490
you see, they're all roughly
around two for the highly

528
00:23:18,490 --> 00:23:24,520
acidic regime, and all around
high nines, low tens for the

529
00:23:24,520 --> 00:23:26,330
alkaline regime.

530
00:23:26,330 --> 00:23:29,290
Roughly the same.

531
00:23:29,290 --> 00:23:29,800
All right.

532
00:23:29,800 --> 00:23:32,650
Now connotation polymerization.

533
00:23:32,650 --> 00:23:34,910
This is the formation
of nylons.

534
00:23:34,910 --> 00:23:38,940
You see how you bond this
mer to the adjacent mer?

535
00:23:38,940 --> 00:23:39,460
Look at this.

536
00:23:39,460 --> 00:23:42,160
The nitrogen, that hydrogen
is sticking up.

537
00:23:42,160 --> 00:23:44,120
There's the nitrogen bonding
to the carbon.

538
00:23:44,120 --> 00:23:45,830
There's a long pair, and
nitrogen-carbon.

539
00:23:48,860 --> 00:23:52,630
Amide bond, peptide
bond, same thing.

540
00:23:52,630 --> 00:23:56,000
The same bond in the backbone
of nylon is the same bond in

541
00:23:56,000 --> 00:23:58,640
the backbone of protein.

542
00:23:58,640 --> 00:24:03,330
Only, the biologists call this
the peptide bond, the polymer

543
00:24:03,330 --> 00:24:06,250
scientists call this
the amide bond.

544
00:24:06,250 --> 00:24:08,990
Think about that when, you know,
the holidays are coming,

545
00:24:08,990 --> 00:24:11,120
you think you're really special,
and you know, the

546
00:24:11,120 --> 00:24:14,880
proteins in your body are really
bound the same way that

547
00:24:14,880 --> 00:24:18,390
nylon is, you know?

548
00:24:18,390 --> 00:24:18,720
All right.

549
00:24:18,720 --> 00:24:20,720
So now let's consider--

550
00:24:20,720 --> 00:24:24,270
and here's some examples.

551
00:24:24,270 --> 00:24:25,830
Here's a peptide.

552
00:24:25,830 --> 00:24:28,020
So it's a long chain here.

553
00:24:28,020 --> 00:24:30,710
So it starts, here's the
amino group, H3N.

554
00:24:30,710 --> 00:24:33,290
It's got glycene, and then
leucine, and valine,

555
00:24:33,290 --> 00:24:34,400
glutamine, et cetera.

556
00:24:34,400 --> 00:24:36,440
So there it goes, all the way
around, around, around,

557
00:24:36,440 --> 00:24:36,750
around, around.

558
00:24:36,750 --> 00:24:37,910
And here's another one.

559
00:24:37,910 --> 00:24:39,810
There's the amino group, and
then, boom, boom, boom.

560
00:24:39,810 --> 00:24:40,940
What's happening here?

561
00:24:40,940 --> 00:24:45,390
All of these click stops
along here are this.

562
00:24:45,390 --> 00:24:46,640
H2NCHCOOH.

563
00:24:48,550 --> 00:24:50,600
And the only thing that's
changing is the R group.

564
00:24:50,600 --> 00:24:52,910
If this were nylon, it
would be the same

565
00:24:52,910 --> 00:24:54,340
thing, all the way down.

566
00:24:54,340 --> 00:24:56,600
That's how this differentiates
itself.

567
00:24:56,600 --> 00:24:59,090
All polymers are
macromolecules.

568
00:24:59,090 --> 00:25:01,100
All macromolecules
are not polymers.

569
00:25:01,100 --> 00:25:04,330
These are not polymers, but
they are macromolecules.

570
00:25:04,330 --> 00:25:06,180
And what else do you see here?

571
00:25:06,180 --> 00:25:06,830
Look at this.

572
00:25:06,830 --> 00:25:10,750
Cysteine happens to have
a double bond.

573
00:25:10,750 --> 00:25:14,140
A residual double bond
in its R group.

574
00:25:14,140 --> 00:25:16,810
Well, where you see a double
bond, you go, I can break the

575
00:25:16,810 --> 00:25:19,850
double bond, and then I can
make a another bond.

576
00:25:19,850 --> 00:25:20,710
And that's what happens.

577
00:25:20,710 --> 00:25:23,520
So we break the double bond with
the sulfur, and now we

578
00:25:23,520 --> 00:25:25,240
make a disulfide linkage.

579
00:25:25,240 --> 00:25:27,120
What do you think the mechanical
properties of this

580
00:25:27,120 --> 00:25:29,360
protein are?

581
00:25:29,360 --> 00:25:32,880
Mechanically, what do you
think this one's like?

582
00:25:32,880 --> 00:25:33,890
It's rubbery.

583
00:25:33,890 --> 00:25:38,200
This is an elastomer, because
you can move the top chain

584
00:25:38,200 --> 00:25:41,250
vis-a-vis the bottom chain until
these disulfide linkages

585
00:25:41,250 --> 00:25:42,690
are flattened.

586
00:25:42,690 --> 00:25:45,890
And then if you let it
go, it springs back.

587
00:25:45,890 --> 00:25:48,070
It's the mechanical properties
of, in this

588
00:25:48,070 --> 00:25:49,320
case, this is insulin.

589
00:25:53,950 --> 00:25:58,540
Now I want to give you a sense
of the variety here.

590
00:25:58,540 --> 00:26:00,520
How much information--

591
00:26:00,520 --> 00:26:04,210
because ultimately, it's all
about reproduction, right?

592
00:26:04,210 --> 00:26:06,120
That's the number one function
of any living

593
00:26:06,120 --> 00:26:08,940
organism, is to reproduce.

594
00:26:08,940 --> 00:26:11,280
That's what makes it life.

595
00:26:11,280 --> 00:26:11,720
Right?

596
00:26:11,720 --> 00:26:13,650
So it needs an instruction
set.

597
00:26:13,650 --> 00:26:15,650
And the instruction set doesn't
come in the box.

598
00:26:15,650 --> 00:26:18,270
It comes inside the organism.

599
00:26:18,270 --> 00:26:19,490
And this is the language.

600
00:26:19,490 --> 00:26:20,950
This is all we have
to work with.

601
00:26:20,950 --> 00:26:22,710
So here's a simple example.

602
00:26:22,710 --> 00:26:27,320
This is, how many combinations
do you have of dipeptides?

603
00:26:27,320 --> 00:26:31,050
So when you start with
two amino acids.

604
00:26:31,050 --> 00:26:34,070
So this is phenylalanine
and aspartic acid.

605
00:26:34,070 --> 00:26:37,830
So if I told you, you have
A and B, and how many AB

606
00:26:37,830 --> 00:26:39,260
mixtures can you come up with?

607
00:26:39,260 --> 00:26:41,670
You'd say, well, you've
got AA, you've got BB,

608
00:26:41,670 --> 00:26:42,660
and you've got AB.

609
00:26:42,660 --> 00:26:44,300
You know, it's sort of
like calculus, right?

610
00:26:44,300 --> 00:26:46,790
If you square A plus B,
you'd get A squared,

611
00:26:46,790 --> 00:26:48,930
plus 2AB, plus B squared.

612
00:26:48,930 --> 00:26:56,060
But because of chirality, AB
is distinguishable from BA.

613
00:26:56,060 --> 00:26:57,240
This is cool.

614
00:26:57,240 --> 00:26:59,510
This is, again, math
serving us, instead

615
00:26:59,510 --> 00:27:02,470
of we serving math.

616
00:27:02,470 --> 00:27:03,190
All right?

617
00:27:03,190 --> 00:27:07,610
So A plus B squared
is A squared

618
00:27:07,610 --> 00:27:10,710
plus 2AB plus B squared.

619
00:27:10,710 --> 00:27:13,270
But no, no, not in biology.

620
00:27:13,270 --> 00:27:16,340
Because AB is chiral,
and therefore

621
00:27:16,340 --> 00:27:19,770
distinguishable from BA.

622
00:27:19,770 --> 00:27:21,410
Now you understand chirality.

623
00:27:21,410 --> 00:27:22,730
So here's--

624
00:27:22,730 --> 00:27:25,490
you get four.

625
00:27:25,490 --> 00:27:30,135
Because see, in this case,
phenylalanine peptide to

626
00:27:30,135 --> 00:27:33,490
aspartic acid is distinguishable
from the one

627
00:27:33,490 --> 00:27:35,370
on the right.

628
00:27:35,370 --> 00:27:36,420
They're distinguishable.

629
00:27:36,420 --> 00:27:38,570
They're different.

630
00:27:38,570 --> 00:27:40,540
OK, so that let's
roll with that.

631
00:27:40,540 --> 00:27:51,500
Let's say, so if I start with
two amino acids, and I want to

632
00:27:51,500 --> 00:27:59,540
make dipeptides, well,
that's trivial.

633
00:27:59,540 --> 00:28:01,590
That's 2 squared, is 4.

634
00:28:01,590 --> 00:28:04,830
So I got four different
dipeptides, starting with two

635
00:28:04,830 --> 00:28:05,660
amino acids.

636
00:28:05,660 --> 00:28:12,330
Now, suppose I said, how many
different dipeptides can we

637
00:28:12,330 --> 00:28:13,350
make, period?

638
00:28:13,350 --> 00:28:16,960
Well, I know I've got a library
of 20 amino acids that

639
00:28:16,960 --> 00:28:18,330
are found in proteins.

640
00:28:18,330 --> 00:28:23,290
So that means the number of
dipeptides would be then 20

641
00:28:23,290 --> 00:28:27,380
squared, which is 400.

642
00:28:27,380 --> 00:28:31,880
But that's hardly
a macromolecule.

643
00:28:31,880 --> 00:28:34,570
So let's get into the
macromolecule business.

644
00:28:34,570 --> 00:28:39,060
So suppose I took a library of
twenty amino acids, and I

645
00:28:39,060 --> 00:28:44,750
said, how many kilopeptides
could I make?

646
00:28:44,750 --> 00:28:46,000
What's a kilopeptide?

647
00:28:46,000 --> 00:28:53,120
A kilopeptide is something
that's got 1000

648
00:28:53,120 --> 00:28:54,670
peptide bonds in it.

649
00:28:54,670 --> 00:29:02,680
So that's going to be 20 to the
power of 1000, which is 10

650
00:29:02,680 --> 00:29:06,590
to the power of 1300.

651
00:29:06,590 --> 00:29:08,480
And this is small.

652
00:29:08,480 --> 00:29:09,820
n equals 1000.

653
00:29:09,820 --> 00:29:12,790
I'm not stretching the point
by pulling something

654
00:29:12,790 --> 00:29:14,100
exceptional out.

655
00:29:14,100 --> 00:29:18,980
A polymer, if it were polymer,
1000 units long, you'd say,

656
00:29:18,980 --> 00:29:21,260
that's sort of fair to
middling length.

657
00:29:21,260 --> 00:29:24,050
I'm not pulling out the longest
polymer ever known.

658
00:29:24,050 --> 00:29:26,870
I didn't go to the Guinness
Book of Records for this.

659
00:29:26,870 --> 00:29:31,120
This is just plain vanilla
mer length.

660
00:29:31,120 --> 00:29:33,410
So look.

661
00:29:33,410 --> 00:29:35,270
How much information
can be contained?

662
00:29:35,270 --> 00:29:37,910
That's in a single element.

663
00:29:37,910 --> 00:29:38,260
OK.

664
00:29:38,260 --> 00:29:41,410
So later on we're going to
return to this, and appreciate

665
00:29:41,410 --> 00:29:45,560
how we can get to such
information density.

666
00:29:45,560 --> 00:29:47,990
And this I think I alluded
to on Wednesday.

667
00:29:47,990 --> 00:29:51,160
These are the three-letter
initializations, and I'll post

668
00:29:51,160 --> 00:29:52,040
this at the website.

669
00:29:52,040 --> 00:29:55,530
So these are the airports that
correspond to the three-letter

670
00:29:55,530 --> 00:29:55,960
initialization.

671
00:29:55,960 --> 00:29:58,850
Then I showed you the one-letter
abbreviation for

672
00:29:58,850 --> 00:30:00,260
each of the peptides.

673
00:30:00,260 --> 00:30:03,160
You know, it's kind of strange,
because the amino

674
00:30:03,160 --> 00:30:04,420
acids are what they are.

675
00:30:04,420 --> 00:30:08,070
And most airports, they're
not like the main ones.

676
00:30:08,070 --> 00:30:10,420
It's not like Boston
or New York.

677
00:30:10,420 --> 00:30:14,560
It's weird places like Australia
and Texas and stuff.

678
00:30:14,560 --> 00:30:14,820
You know?

679
00:30:14,820 --> 00:30:16,070
So--

680
00:30:17,750 --> 00:30:19,300
hey, you've got to have
a sense of humor!

681
00:30:19,300 --> 00:30:20,910
Come on.

682
00:30:20,910 --> 00:30:21,180
All right.

683
00:30:21,180 --> 00:30:22,700
And there's glutamic acid.

684
00:30:22,700 --> 00:30:28,270
There's no airport that has
GLU as its three-letter--

685
00:30:28,270 --> 00:30:29,220
OK.

686
00:30:29,220 --> 00:30:30,300
So here we are.

687
00:30:30,300 --> 00:30:31,780
So now we want to do
is want to talk

688
00:30:31,780 --> 00:30:33,030
about protein structure.

689
00:30:35,290 --> 00:30:38,030
And so we're going to look at
this as material scientists.

690
00:30:38,030 --> 00:30:40,610
We're not going to look at it
the way chemists, capital

691
00:30:40,610 --> 00:30:41,340
C-chemists, do.

692
00:30:41,340 --> 00:30:44,590
And I think by looking at it
from a structure perspective,

693
00:30:44,590 --> 00:30:46,200
you get some insights
into what we can

694
00:30:46,200 --> 00:30:47,200
do with these things.

695
00:30:47,200 --> 00:30:48,450
So protein structure.

696
00:30:52,470 --> 00:30:54,660
And I'm going to use the
terminology that the

697
00:30:54,660 --> 00:30:55,530
biologists use.

698
00:30:55,530 --> 00:30:57,600
So first of all, they have
something they call the

699
00:30:57,600 --> 00:31:01,090
primary structure
of the protein.

700
00:31:01,090 --> 00:31:04,990
And it speaks to composition,
the composition.

701
00:31:04,990 --> 00:31:06,220
Well, what's the composition?

702
00:31:06,220 --> 00:31:09,320
We know that every protein is
made of amino acids, and every

703
00:31:09,320 --> 00:31:10,720
amino acid is virtually
identical,

704
00:31:10,720 --> 00:31:13,410
except for the R group.

705
00:31:13,410 --> 00:31:15,080
So when you say the composition,
you're really

706
00:31:15,080 --> 00:31:18,660
saying, what is the
R sequence?

707
00:31:18,660 --> 00:31:24,900
It's the amino acid sequence
down the backbone.

708
00:31:24,900 --> 00:31:27,350
Because you've polymerized
this thing, or

709
00:31:27,350 --> 00:31:29,140
macromolecularized it.

710
00:31:29,140 --> 00:31:33,646
Amino acid sequence, which
along the backbone.

711
00:31:38,330 --> 00:31:43,370
Which is really the R groups.

712
00:31:43,370 --> 00:31:45,360
The sequence of R groups,
which is going to be the

713
00:31:45,360 --> 00:31:46,930
sequence, OK?

714
00:31:46,930 --> 00:31:47,310
All right.

715
00:31:47,310 --> 00:31:48,440
So here you can see.

716
00:31:48,440 --> 00:31:50,900
There's an amino
acid sequence.

717
00:31:50,900 --> 00:31:52,470
Number two is the--

718
00:31:52,470 --> 00:31:54,490
these are really--

719
00:31:54,490 --> 00:31:57,820
you know, like the polymer
people had conformality.

720
00:31:57,820 --> 00:32:01,050
You know, they had nice,
powerful words.

721
00:32:01,050 --> 00:32:03,100
The first order is the primary,
and then the second

722
00:32:03,100 --> 00:32:05,110
one is the secondary.

723
00:32:05,110 --> 00:32:08,050
I'm trying to make fun of the
biologists, and you're sitting

724
00:32:08,050 --> 00:32:10,900
there, you know, with that
same Thanksgiving

725
00:32:10,900 --> 00:32:13,790
dinner table stoicism.

726
00:32:13,790 --> 00:32:14,050
OK.

727
00:32:14,050 --> 00:32:15,400
So what's the secondary?

728
00:32:15,400 --> 00:32:20,560
The secondary structure of
proteins speaks to packing.

729
00:32:25,840 --> 00:32:28,930
And what's the gambit here?

730
00:32:28,930 --> 00:32:30,780
Why do they pack in
different ways?

731
00:32:30,780 --> 00:32:32,280
Well, just as we saw,
you can have a long

732
00:32:32,280 --> 00:32:33,680
chain, straight chain.

733
00:32:33,680 --> 00:32:35,930
Sometimes things full
back on themselves.

734
00:32:35,930 --> 00:32:38,380
It's still a straight chain, but
there's a curve, a bend in

735
00:32:38,380 --> 00:32:39,470
it, and so on.

736
00:32:39,470 --> 00:32:44,460
What proteins are going to do in
order to pack, is to try to

737
00:32:44,460 --> 00:32:46,480
maximize hydrogen bonding.

738
00:32:51,630 --> 00:32:53,070
And this is not even
between proteins.

739
00:32:53,070 --> 00:32:56,190
This is a protein forming
on itself.

740
00:32:56,190 --> 00:32:59,780
And you could argue, why do you
maximize hydrogen bonding?

741
00:32:59,780 --> 00:33:02,640
Because when you make more bonds
per unit volume, you

742
00:33:02,640 --> 00:33:04,160
decrease the energy
of a system.

743
00:33:04,160 --> 00:33:06,600
You've been taught that
over and over again.

744
00:33:06,600 --> 00:33:09,720
So these are long chain
molecules, but they still can

745
00:33:09,720 --> 00:33:11,400
loop back on one another.

746
00:33:11,400 --> 00:33:16,360
And if you've got a choice of
forming a dipole-dipole

747
00:33:16,360 --> 00:33:20,280
interaction, a induced
dipole-induced dipole

748
00:33:20,280 --> 00:33:23,580
interaction, or a hydrogen bond,
which is going to give

749
00:33:23,580 --> 00:33:27,510
you the most decrease
per unit bond?

750
00:33:27,510 --> 00:33:28,460
It's hydrogen.

751
00:33:28,460 --> 00:33:31,680
So if you can form hydrogen
bonds, that gives you the most

752
00:33:31,680 --> 00:33:33,380
impact per bond.

753
00:33:33,380 --> 00:33:36,210
If you don't have hydrogen
bonding capability, then you

754
00:33:36,210 --> 00:33:38,160
go for dipole-dipole.

755
00:33:38,160 --> 00:33:40,290
And if you don't have
dipole-dipole, then it's just

756
00:33:40,290 --> 00:33:43,640
the weak van der Waals, or
the London dispersion.

757
00:33:43,640 --> 00:33:46,280
So that's why this thing goes
for hydrogen bonding.

758
00:33:46,280 --> 00:33:47,930
Because it wants to.

759
00:33:47,930 --> 00:33:49,410
It wants to decrease
the energy.

760
00:33:49,410 --> 00:33:52,230
So I have to show you
a few cartoons here.

761
00:33:52,230 --> 00:33:52,530
All right.

762
00:33:52,530 --> 00:33:56,520
So here's a sketch taken from
one of the readings.

763
00:33:56,520 --> 00:33:58,920
So there's alpha carbon.

764
00:33:58,920 --> 00:34:01,960
This is the carboxylic
acid, right here.

765
00:34:01,960 --> 00:34:04,860
And this is the peptide bond
between one carbon and a

766
00:34:04,860 --> 00:34:08,880
nitrogen in an adjacent unit.

767
00:34:08,880 --> 00:34:09,460
All right?

768
00:34:09,460 --> 00:34:11,050
So there's the peptide bond.

769
00:34:11,050 --> 00:34:13,690
The interesting thing is that
even though this is sp3

770
00:34:13,690 --> 00:34:19,000
hybridized, data show that all
six atoms lie in a plane.

771
00:34:19,000 --> 00:34:20,930
So what happened last
time when we came

772
00:34:20,930 --> 00:34:22,220
up with this conundrum?

773
00:34:22,220 --> 00:34:25,630
sp3 hybridized, but the data
showed it all lies in a plane.

774
00:34:25,630 --> 00:34:27,030
That was benzene, remember?

775
00:34:27,030 --> 00:34:30,040
And how do we skate with
the puck on benzene?

776
00:34:30,040 --> 00:34:31,050
Resonance.

777
00:34:31,050 --> 00:34:35,370
We said it resonates between two
structures, and sometimes

778
00:34:35,370 --> 00:34:37,480
the nitrogen lies
in the plane.

779
00:34:37,480 --> 00:34:39,540
Sometimes the alpha carbon
lies in the plane.

780
00:34:39,540 --> 00:34:41,860
But thanks to resonance,
all six of these

781
00:34:41,860 --> 00:34:43,450
can lie in the plane.

782
00:34:43,450 --> 00:34:43,800
OK.

783
00:34:43,800 --> 00:34:47,960
So now how do we get to
hydrogen bonding?

784
00:34:47,960 --> 00:34:49,558
So there's the resonance.

785
00:34:49,558 --> 00:34:49,976
All right.

786
00:34:49,976 --> 00:34:51,650
Good.

787
00:34:51,650 --> 00:34:54,030
So you see, this is free
to rotate, right?

788
00:34:54,030 --> 00:34:57,300
Once we accept that these six
atoms line in a plane, and

789
00:34:57,300 --> 00:35:00,680
these six atoms line in a plane,
and 109 degree angle is

790
00:35:00,680 --> 00:35:04,020
fixed, but there's that degree
of rotation, which is what

791
00:35:04,020 --> 00:35:08,400
gave us the original C17H36
folding back on itself, only

792
00:35:08,400 --> 00:35:12,530
we're going to fold back on
ourselves in groups of six.

793
00:35:12,530 --> 00:35:13,850
So we've got a deck
of cards here.

794
00:35:13,850 --> 00:35:16,420
I've got six here, six
here, six here.

795
00:35:16,420 --> 00:35:17,510
So what am I going to do?

796
00:35:17,510 --> 00:35:23,050
I'm going to try to make this
blue plane lie relative to the

797
00:35:23,050 --> 00:35:27,910
yellow plane in such a way as to
maximize hydrogen bonding.

798
00:35:27,910 --> 00:35:31,720
Speaking of energy deficit,
we need battery.

799
00:35:31,720 --> 00:35:32,650
All right, here we go.

800
00:35:32,650 --> 00:35:33,870
So now we're going
to maximize.

801
00:35:33,870 --> 00:35:34,130
Look.

802
00:35:34,130 --> 00:35:38,780
You see, if I rotate this blue
plane in just the right way, I

803
00:35:38,780 --> 00:35:41,440
can set up to have a hydrogen
bond form between this

804
00:35:41,440 --> 00:35:47,550
hydrogen and this oxygen, and on
the orange plane, an oxygen

805
00:35:47,550 --> 00:35:48,850
and a hydrogen.

806
00:35:48,850 --> 00:35:51,680
So now it becomes a matter
of figuring out,

807
00:35:51,680 --> 00:35:52,890
what are these angles?

808
00:35:52,890 --> 00:35:54,790
You see, there's a phi
and a psi here.

809
00:35:54,790 --> 00:35:58,350
What are the angles phi and
psi to give the maximum

810
00:35:58,350 --> 00:36:05,320
hydrogen bonding between these
two six-packs of atoms?

811
00:36:05,320 --> 00:36:07,720
And from that, you get
secondary structure.

812
00:36:07,720 --> 00:36:10,100
It's all about maximizing
hydrogen bonding.

813
00:36:10,100 --> 00:36:11,750
After that, if you understand
what I just

814
00:36:11,750 --> 00:36:13,940
said, the rest is trivia.

815
00:36:16,755 --> 00:36:18,350
So here's what happens.

816
00:36:18,350 --> 00:36:19,860
Here's one structure.

817
00:36:19,860 --> 00:36:26,230
And this was first discovered,
if you like, revealed, by

818
00:36:26,230 --> 00:36:27,890
Linus Pauling, 1951.

819
00:36:27,890 --> 00:36:33,070
Linus Pauling and Corey, 1951,
came with the realization that

820
00:36:33,070 --> 00:36:39,620
if the protein spirals in a
helix, it will line up the

821
00:36:39,620 --> 00:36:43,120
maximum number of
hydrogen-oxygen hydrogen

822
00:36:43,120 --> 00:36:46,830
bonding opportunities, as
opposed to going straight.

823
00:36:46,830 --> 00:36:50,860
So it doesn't go perfectly
straight, it coils.

824
00:36:50,860 --> 00:36:53,030
And this is two different
cartoons trying to show.

825
00:36:53,030 --> 00:36:57,000
So you can see peptide bonds,
and then every so often you

826
00:36:57,000 --> 00:36:58,070
get a hydrogen-oxyge bond.

827
00:36:58,070 --> 00:37:01,600
Because it spins around, and
the idea is, as the helix

828
00:37:01,600 --> 00:37:04,020
forms, you can think of it as--
have you ever gone up a

829
00:37:04,020 --> 00:37:05,390
spiral staircase?

830
00:37:05,390 --> 00:37:09,400
And you think of each subsequent
turn of the spiral

831
00:37:09,400 --> 00:37:11,060
as a new gallery.

832
00:37:11,060 --> 00:37:12,270
And what you've got is hydrogen

833
00:37:12,270 --> 00:37:14,060
bonds between the galleries.

834
00:37:14,060 --> 00:37:16,385
So you're going up, and there's
a hydrogen bond here,

835
00:37:16,385 --> 00:37:18,480
and you keep turning, and
there's a hydrogen bond here,

836
00:37:18,480 --> 00:37:20,070
and there's a hydrogen
bond here.

837
00:37:20,070 --> 00:37:22,160
That's the way to get maximum
hydrogen bonding.

838
00:37:22,160 --> 00:37:24,700
There it is.

839
00:37:24,700 --> 00:37:26,100
There's another example.

840
00:37:26,100 --> 00:37:28,200
Maybe this is a nicer one.

841
00:37:28,200 --> 00:37:30,800
And there's 3.6 residues
per turn.

842
00:37:30,800 --> 00:37:36,850
That means, per turn is 3.6 R
groups, which, it's called

843
00:37:36,850 --> 00:37:39,500
residues because historically,
when people did the chemical

844
00:37:39,500 --> 00:37:42,740
analysis, the residue contained
the substituent.

845
00:37:42,740 --> 00:37:44,410
That's how they determined
what the identity of the

846
00:37:44,410 --> 00:37:45,440
protein is.

847
00:37:45,440 --> 00:37:46,930
They can't just look at it.

848
00:37:46,930 --> 00:37:49,060
And you can't use
spectroscopy.

849
00:37:49,060 --> 00:37:50,890
Maybe now you can, but
in the old days--

850
00:37:50,890 --> 00:37:52,290
I mean, these are all, look.

851
00:37:52,290 --> 00:37:52,880
Low mass.

852
00:37:52,880 --> 00:37:54,790
Hydrogen, oxygen, nitrogen.

853
00:37:54,790 --> 00:37:56,050
They're not distinguishable.

854
00:37:56,050 --> 00:37:57,810
They're all low-Z elements.

855
00:37:57,810 --> 00:38:00,630
So they had to do wet chemistry,
and they would

856
00:38:00,630 --> 00:38:03,710
actually peel off the
R groups, which

857
00:38:03,710 --> 00:38:04,690
were called the residuals.

858
00:38:04,690 --> 00:38:07,270
And so 3.6 residuals
per turn give you

859
00:38:07,270 --> 00:38:09,400
this alpha helix structure.

860
00:38:09,400 --> 00:38:11,590
there's a second structure
that works.

861
00:38:11,590 --> 00:38:15,020
The second structure is
between two chains.

862
00:38:15,020 --> 00:38:18,560
So in this case, instead of
going coiling by yourself, and

863
00:38:18,560 --> 00:38:21,370
forming the galleries, what you
do is you take two chains

864
00:38:21,370 --> 00:38:25,190
side by side, and you pace them
so that you get maximum

865
00:38:25,190 --> 00:38:26,400
amount of hydrogen bonding.

866
00:38:26,400 --> 00:38:30,400
I showed you this with nylon,
how two strands

867
00:38:30,400 --> 00:38:31,840
of nylon bond together.

868
00:38:31,840 --> 00:38:33,730
They can form hydrogen bonds.

869
00:38:33,730 --> 00:38:34,920
Same thing here.

870
00:38:34,920 --> 00:38:41,200
And now, since these are jerking
in a motion of six in

871
00:38:41,200 --> 00:38:45,570
a plane, six in a plane, six
in a plane, six in a plane,

872
00:38:45,570 --> 00:38:47,730
what you end up with
is this pleating.

873
00:38:47,730 --> 00:38:48,520
It's hard to see here.

874
00:38:48,520 --> 00:38:50,980
Maybe if your eye can follow
along the top here.

875
00:38:50,980 --> 00:38:54,370
Here's sort of a cream-colored
one, orangey-cream, and it's

876
00:38:54,370 --> 00:38:57,830
moving sort of southwest to
northeast. And here's one

877
00:38:57,830 --> 00:39:01,020
that's sort of a grayish, and
it's moving from northwest to

878
00:39:01,020 --> 00:39:03,350
southeast. And then
up, and then down.

879
00:39:03,350 --> 00:39:05,570
And zig and then zag.

880
00:39:05,570 --> 00:39:07,340
And this is called the
pleated sheet.

881
00:39:07,340 --> 00:39:08,660
This is the beta form.

882
00:39:08,660 --> 00:39:11,985
The alpha form is the helix,
and the beta form is the

883
00:39:11,985 --> 00:39:12,860
pleated sheet.

884
00:39:12,860 --> 00:39:15,970
Same thing up here in a
different kind of model.

885
00:39:15,970 --> 00:39:18,930
Which I look at that and I go,
I don't get any information

886
00:39:18,930 --> 00:39:20,310
from this thing at all.

887
00:39:20,310 --> 00:39:21,340
But they put it in the books.

888
00:39:21,340 --> 00:39:21,950
Who cares.

889
00:39:21,950 --> 00:39:24,010
This is where you learn
something, right here.

890
00:39:24,010 --> 00:39:27,400
Once you appreciate that those
six atoms have to be in a

891
00:39:27,400 --> 00:39:30,000
plane, and how to maximize
hydrogen bonding.

892
00:39:30,000 --> 00:39:33,310
So let's put that down.

893
00:39:33,310 --> 00:39:34,560
This is all Linus Pauling.

894
00:39:37,010 --> 00:39:38,410
So secondary.

895
00:39:38,410 --> 00:39:44,090
So you know that six
atoms in plane,

896
00:39:44,090 --> 00:39:47,690
which leads to resonance.

897
00:39:47,690 --> 00:39:51,310
And now, from there, you just
needs the genius of Linus

898
00:39:51,310 --> 00:39:54,600
Pauling, and then you conclude
that to maximize hydrogen

899
00:39:54,600 --> 00:40:01,310
bonding, you form the alpha
helix with hydrogen bonding

900
00:40:01,310 --> 00:40:02,560
between galleries.

901
00:40:08,020 --> 00:40:08,360
All right?

902
00:40:08,360 --> 00:40:12,290
And then the second one is the
pleated sheet, or people just

903
00:40:12,290 --> 00:40:13,145
call it the sheet.

904
00:40:13,145 --> 00:40:15,310
But to me, the sheet
means nothing!

905
00:40:15,310 --> 00:40:17,470
It's the fact that
it's pleated.

906
00:40:17,470 --> 00:40:21,190
So I'm going to ignore
what the books say.

907
00:40:21,190 --> 00:40:25,700
Pleated, pleated sheet.

908
00:40:25,700 --> 00:40:26,010
OK.

909
00:40:26,010 --> 00:40:29,710
So this is hydrogen
bonds between

910
00:40:29,710 --> 00:40:35,370
galleries of the same protein.

911
00:40:35,370 --> 00:40:41,230
Whereas this is hydrogen
bonding between

912
00:40:41,230 --> 00:40:42,480
macromolecules.

913
00:40:46,070 --> 00:40:48,560
So if they're both pleated,
it's going to work.

914
00:40:48,560 --> 00:40:53,790
Or of course, that could be
folding back on itself.

915
00:40:53,790 --> 00:40:55,690
Remember how I showed you the
first day the chain, how the

916
00:40:55,690 --> 00:40:58,640
chain wanted to zig-zag,
to crystallize?

917
00:40:58,640 --> 00:41:00,680
Do you think protein
is liable to fold?

918
00:41:00,680 --> 00:41:02,250
You've heard of protein
folding?

919
00:41:02,250 --> 00:41:03,480
Why does it fold?

920
00:41:03,480 --> 00:41:06,430
Because it wants to maximize
hydrogen bonding!

921
00:41:06,430 --> 00:41:09,040
And when it folds, it's not
going to maximize hydrogen

922
00:41:09,040 --> 00:41:12,060
bonding unless it is in
the beta pleated sheet

923
00:41:12,060 --> 00:41:12,680
arrangement.

924
00:41:12,680 --> 00:41:14,250
Otherwise, what's the
point of folding?

925
00:41:14,250 --> 00:41:15,560
Because you can't
make the link.

926
00:41:15,560 --> 00:41:18,110
Because I'm the oxygen, the
hydrogen's way over there.

927
00:41:18,110 --> 00:41:20,040
If that hydrogen were
right over here, we

928
00:41:20,040 --> 00:41:21,290
could form the bond.

929
00:41:24,090 --> 00:41:25,530
And then the third
one is random.

930
00:41:29,080 --> 00:41:30,180
So let's take a look.

931
00:41:30,180 --> 00:41:34,160
I think I've got some
images here.

932
00:41:34,160 --> 00:41:35,870
Oh, here's another one,
showing the-- yeah.

933
00:41:38,420 --> 00:41:40,070
I'm trying to, I'm really
working hard.

934
00:41:40,070 --> 00:41:42,112
Here's six, here's six,
here's six, and

935
00:41:42,112 --> 00:41:44,060
there's the common carbon.

936
00:41:44,060 --> 00:41:44,720
OK?

937
00:41:44,720 --> 00:41:45,990
And now you can see
the hydrogen

938
00:41:45,990 --> 00:41:47,120
bonds forming between.

939
00:41:47,120 --> 00:41:50,080
So this could be one protein,
this could be another protein,

940
00:41:50,080 --> 00:41:53,450
or this could be the same
protein that's folding back on

941
00:41:53,450 --> 00:41:56,285
itself in a
pseudo-crystallization ploy.

942
00:41:59,520 --> 00:42:00,950
Yeah.

943
00:42:00,950 --> 00:42:01,240
All right.

944
00:42:01,240 --> 00:42:03,260
So if you look in the biology
literature, you'll see

945
00:42:03,260 --> 00:42:05,120
drawings like this.

946
00:42:05,120 --> 00:42:06,340
You've seen these, huh?

947
00:42:06,340 --> 00:42:08,310
You look at them and go, what
are they talking about?

948
00:42:08,310 --> 00:42:09,310
Now you know!

949
00:42:09,310 --> 00:42:11,630
This is the secondary
structure.

950
00:42:11,630 --> 00:42:14,510
Let's start over here
at the amino end.

951
00:42:14,510 --> 00:42:16,760
So you're moving along, and it's
just sort of random, and

952
00:42:16,760 --> 00:42:18,510
now, all of a sudden, look.

953
00:42:18,510 --> 00:42:19,960
Round and round and round.

954
00:42:19,960 --> 00:42:21,240
What are you looking at?

955
00:42:21,240 --> 00:42:26,090
For this run of length, it's
in the alpha helix form!

956
00:42:26,090 --> 00:42:28,320
And then it kind of goes random
for a little bit, and

957
00:42:28,320 --> 00:42:29,560
then it goes green.

958
00:42:29,560 --> 00:42:33,730
And this green area
is pleated sheet.

959
00:42:33,730 --> 00:42:35,720
So if the pleated sheet goes
this way, and then it goes

960
00:42:35,720 --> 00:42:37,710
random, and then the pleated
sheet goes this way, what's

961
00:42:37,710 --> 00:42:39,870
going to happen? there's going
to be hydrogen bonding here,

962
00:42:39,870 --> 00:42:42,520
hydrogen bonding here, hydrogen
bonding here.

963
00:42:42,520 --> 00:42:46,100
And you know, how is it that
this thing decides, oh,

964
00:42:46,100 --> 00:42:47,410
somewhere around
here, I think.

965
00:42:47,410 --> 00:42:51,190
I think I'll just go into an
alpha helix arrangement.

966
00:42:51,190 --> 00:42:54,110
Why is it alpha helix here,
and not alpha helix here?

967
00:42:58,720 --> 00:43:02,430
Because of the instant
choice of R groups!

968
00:43:02,430 --> 00:43:06,190
The instant choice of R groups
will dictate whether it can

969
00:43:06,190 --> 00:43:07,440
turn around.

970
00:43:07,440 --> 00:43:10,240
Because if you've got glycene
with its dinky little hydrogen

971
00:43:10,240 --> 00:43:13,730
on one side, you're compact
and you can move around.

972
00:43:13,730 --> 00:43:17,800
But some of these other pendant
groups are big, and

973
00:43:17,800 --> 00:43:20,460
you can't just shove them
one into the other.

974
00:43:20,460 --> 00:43:22,530
They'll repel.

975
00:43:22,530 --> 00:43:23,820
They won't fit.

976
00:43:23,820 --> 00:43:25,490
So this dictates--

977
00:43:25,490 --> 00:43:30,730
so in essence, the secondary
structure is set, the table is

978
00:43:30,730 --> 00:43:32,690
set by the primary structure,
isn't it?

979
00:43:35,860 --> 00:43:39,410
This is so cool.

980
00:43:39,410 --> 00:43:44,010
Then there's the tertiary
structure.

981
00:43:44,010 --> 00:43:47,340
Because random isn't, as they
say in California, it's not

982
00:43:47,340 --> 00:43:48,800
totally random.

983
00:43:48,800 --> 00:43:51,800
There's some order to it.

984
00:43:51,800 --> 00:43:53,780
So let's look at the
order that comes.

985
00:43:53,780 --> 00:43:54,240
See this?

986
00:43:54,240 --> 00:43:55,100
Look over here.

987
00:43:55,100 --> 00:43:56,200
You see up here?

988
00:43:56,200 --> 00:43:57,450
This is supposed to
be random coil.

989
00:43:57,450 --> 00:43:59,290
But look at it.

990
00:43:59,290 --> 00:44:01,230
It's kind of dentate
there, isn't it.

991
00:44:01,230 --> 00:44:02,530
See, it's sort of tooth-like.

992
00:44:02,530 --> 00:44:04,800
Do you think that the artist
just did that?

993
00:44:04,800 --> 00:44:07,160
Why is it like that?

994
00:44:07,160 --> 00:44:09,750
Because of the molecular
forces!

995
00:44:09,750 --> 00:44:11,240
So let's think on it.

996
00:44:11,240 --> 00:44:12,600
Oh!

997
00:44:12,600 --> 00:44:15,760
This is a little piece
from Guys and Dolls.

998
00:44:15,760 --> 00:44:16,940
1951.

999
00:44:16,940 --> 00:44:20,120
The same your Pauling
enunciated this.

1000
00:44:20,120 --> 00:44:22,010
I bet you think that when
people talk about the

1001
00:44:22,010 --> 00:44:27,300
chemistry between folks, that
it's a '60s phenomenon.

1002
00:44:27,300 --> 00:44:29,230
You know, the hippies,
drug culture.

1003
00:44:29,230 --> 00:44:29,665
No.

1004
00:44:29,665 --> 00:44:30,850
It goes way back.

1005
00:44:30,850 --> 00:44:31,680
Goes to the '50s.

1006
00:44:31,680 --> 00:44:34,900
Listen to this.

1007
00:44:34,900 --> 00:44:38,460
This Sky Masterson, and he's
going to tell Sarah-- she's

1008
00:44:38,460 --> 00:44:41,440
the one that's the,
she plays the--

1009
00:44:41,440 --> 00:44:42,640
what do you call it--

1010
00:44:42,640 --> 00:44:45,550
she works at the Salvation
Army mission.

1011
00:44:45,550 --> 00:44:47,605
And he's a gambler, which in
those days was really, you

1012
00:44:47,605 --> 00:44:48,370
know, like low-life.

1013
00:44:48,370 --> 00:44:50,040
And he's flirting with her,
and she, of course, has

1014
00:44:50,040 --> 00:44:51,450
nothing to do with him,
and eventually, they

1015
00:44:51,450 --> 00:44:52,280
fall in love, of course.

1016
00:44:52,280 --> 00:44:56,350
But anyway, so she's told him
how she's going to meet the

1017
00:44:56,350 --> 00:44:57,360
man of her life.

1018
00:44:57,360 --> 00:44:58,210
And she's very linear.

1019
00:44:58,210 --> 00:45:00,020
He's got all of these
characteristics, and

1020
00:45:00,020 --> 00:45:00,780
so on and so forth.

1021
00:45:00,780 --> 00:45:01,920
Real linear.

1022
00:45:01,920 --> 00:45:04,790
And this guy's a gambler, so
he's going to tell her how

1023
00:45:04,790 --> 00:45:06,685
he's going to find the
love of his life.

1024
00:45:06,685 --> 00:45:07,130
[BEGIN FILM PLAYBACK]

1025
00:45:07,130 --> 00:45:09,310
Do you want to hear how a
gambler feels about the big

1026
00:45:09,310 --> 00:45:09,760
heart drop?

1027
00:45:09,760 --> 00:45:10,880
No!

1028
00:45:10,880 --> 00:45:12,550
Well, I'll tell you.

1029
00:45:12,550 --> 00:45:16,050
Mine will come as a
surprise to me.

1030
00:45:16,050 --> 00:45:20,421
Mine, I leave to chance
and chemistry?

1031
00:45:20,421 --> 00:45:21,420
Chemistry?

1032
00:45:21,420 --> 00:45:24,590
Yeah, chemistry.

1033
00:45:24,590 --> 00:45:29,044
Suddenly I'll know when
my love comes along.

1034
00:45:29,044 --> 00:45:29,536
I'll know--

1035
00:45:29,536 --> 00:45:30,030
[END FILM PLAYBACK]

1036
00:45:30,030 --> 00:45:30,530
So there you have it.

1037
00:45:30,530 --> 00:45:31,630
From 1951.

1038
00:45:31,630 --> 00:45:34,590
Chemistry, again, chemistry!

1039
00:45:34,590 --> 00:45:36,540
Chemistry is the central thing.

1040
00:45:36,540 --> 00:45:36,790
OK.

1041
00:45:36,790 --> 00:45:38,060
Now let's go forward.

1042
00:45:38,060 --> 00:45:38,310
All right.

1043
00:45:38,310 --> 00:45:40,680
So now let's figure out why--

1044
00:45:40,680 --> 00:45:44,140
and now I want to answer the
question, why is this forming

1045
00:45:44,140 --> 00:45:45,670
a tooth-like structure?

1046
00:45:45,670 --> 00:45:46,680
Why?

1047
00:45:46,680 --> 00:45:48,880
There's a reason
for everything.

1048
00:45:48,880 --> 00:45:49,300
All right.

1049
00:45:49,300 --> 00:45:52,900
So here we are, moving along
a length of random coils.

1050
00:45:52,900 --> 00:45:55,570
So we're in zone three
here, random.

1051
00:45:55,570 --> 00:45:57,520
But it's not completely
random.

1052
00:45:57,520 --> 00:46:00,540
So this is the tertiary
structure, and it has to do

1053
00:46:00,540 --> 00:46:04,910
with interactions between
the R groups.

1054
00:46:04,910 --> 00:46:07,760
So let's look at number
one, zone one here.

1055
00:46:07,760 --> 00:46:11,270
We've got two cysteines,
and cysteine both

1056
00:46:11,270 --> 00:46:13,220
have sulfur in them.

1057
00:46:13,220 --> 00:46:17,750
It turns out that the sulfurs
can form a covalent bond here.

1058
00:46:17,750 --> 00:46:20,410
This is between two
R groups along a

1059
00:46:20,410 --> 00:46:21,570
certain length of chain.

1060
00:46:21,570 --> 00:46:24,840
And once that covalent bond
forms, this chain now can't

1061
00:46:24,840 --> 00:46:27,100
just go flopping any which
way, because it's

1062
00:46:27,100 --> 00:46:28,480
being held in place.

1063
00:46:28,480 --> 00:46:31,350
It's like you put
a prop there.

1064
00:46:31,350 --> 00:46:33,690
Over here, what do we
have in zone two?

1065
00:46:33,690 --> 00:46:39,760
We have one R group that's
got a hydroxyl.

1066
00:46:39,760 --> 00:46:40,950
Another one's got an oxygen.

1067
00:46:40,950 --> 00:46:44,360
There's a hydrogen bond forming
between side groups.

1068
00:46:44,360 --> 00:46:47,020
And in order to form that
hydrogen bond, can you see

1069
00:46:47,020 --> 00:46:49,310
that this coil is
actually bent?

1070
00:46:49,310 --> 00:46:51,040
You see, there's a kink here.

1071
00:46:51,040 --> 00:46:53,340
This coil should be
much longer, if it

1072
00:46:53,340 --> 00:46:55,450
were straight, distended.

1073
00:46:55,450 --> 00:46:59,050
But it's actually compressed
a little bit in order to

1074
00:46:59,050 --> 00:47:01,480
facilitate the formation
of this hydrogen bond.

1075
00:47:01,480 --> 00:47:04,780
Which means now, this coil
will stay in this

1076
00:47:04,780 --> 00:47:06,290
configuration.

1077
00:47:06,290 --> 00:47:07,960
And then over here,
what do we have?

1078
00:47:07,960 --> 00:47:10,430
Here we have a substituent group
that's net positive,

1079
00:47:10,430 --> 00:47:12,750
here we have a substituent group
that's net negative, and

1080
00:47:12,750 --> 00:47:15,260
we have an electrostatic
force.

1081
00:47:15,260 --> 00:47:16,130
This is coulombic.

1082
00:47:16,130 --> 00:47:18,340
This is plus attracts minus.

1083
00:47:18,340 --> 00:47:20,970
And they form.

1084
00:47:20,970 --> 00:47:23,700
And over here, this is
very interesting.

1085
00:47:23,700 --> 00:47:24,490
What do we have here?

1086
00:47:24,490 --> 00:47:27,500
We have a whole bunch of R
groups that are all non-polar.

1087
00:47:27,500 --> 00:47:30,110
And this thing's sitting
in an aqueous solution.

1088
00:47:30,110 --> 00:47:33,500
And what do you know about
non-polar groups in water?

1089
00:47:33,500 --> 00:47:35,230
They're hydrophobic!

1090
00:47:35,230 --> 00:47:37,830
So I've got this one
hydrophobic group

1091
00:47:37,830 --> 00:47:39,000
sticking out over here.

1092
00:47:39,000 --> 00:47:41,140
It's just going to
have to take it.

1093
00:47:41,140 --> 00:47:43,120
Because it's bound
to the backbone.

1094
00:47:43,120 --> 00:47:45,360
But I've got another
one over here, and

1095
00:47:45,360 --> 00:47:46,700
the backbone is flexible.

1096
00:47:46,700 --> 00:47:48,930
And I've got another
one over here.

1097
00:47:48,930 --> 00:47:53,220
Can you see that if the backbone
folds around, I can

1098
00:47:53,220 --> 00:47:58,100
collect all the hydrophobic
entities, and present to the

1099
00:47:58,100 --> 00:48:02,300
water the hydrophilic opposite
side of the backbone.

1100
00:48:02,300 --> 00:48:05,300
Because if the R group here is
hydrophobic, look what's on

1101
00:48:05,300 --> 00:48:06,740
the other side.

1102
00:48:06,740 --> 00:48:07,800
These guys.

1103
00:48:07,800 --> 00:48:11,610
So if I can take all of these
and cluster them, then I sort

1104
00:48:11,610 --> 00:48:12,960
of minimize the energy.

1105
00:48:12,960 --> 00:48:16,380
Because that there is a
repulsive energy term, right?

1106
00:48:16,380 --> 00:48:19,700
The water doesn't like the
non-polar R group.

1107
00:48:19,700 --> 00:48:22,390
So let's minimize their
contact, you know?

1108
00:48:22,390 --> 00:48:24,320
If you've got two siblings that
are fighting, you put

1109
00:48:24,320 --> 00:48:25,660
them at the other end
of the table.

1110
00:48:25,660 --> 00:48:27,450
You don't sit them next
to one another.

1111
00:48:27,450 --> 00:48:28,390
So here's what you do.

1112
00:48:28,390 --> 00:48:31,490
You cluster all of this
stuff, and that

1113
00:48:31,490 --> 00:48:34,780
causes big hairpin turn.

1114
00:48:34,780 --> 00:48:37,555
So this is called hydrophobic
interactions.

1115
00:48:41,570 --> 00:48:43,000
And that's the tertiary
structure.

1116
00:48:45,940 --> 00:48:48,150
So you see all of those.

1117
00:48:48,150 --> 00:48:49,860
That's great.

1118
00:48:49,860 --> 00:48:51,080
OK.

1119
00:48:51,080 --> 00:48:53,560
I see we're getting close
to the witching hour.

1120
00:48:53,560 --> 00:48:56,760
So maybe I'll teach you how to
do your laundry and send you

1121
00:48:56,760 --> 00:48:57,650
on your way.

1122
00:48:57,650 --> 00:49:03,020
So this interaction I'm just
showing you right here is the

1123
00:49:03,020 --> 00:49:06,860
same thing that's happening
when you do your laundry.

1124
00:49:06,860 --> 00:49:07,760
Now, what's a detergent?

1125
00:49:07,760 --> 00:49:12,490
A detergent is this long
molecule that's got-- you see

1126
00:49:12,490 --> 00:49:13,560
this zig-zag here?

1127
00:49:13,560 --> 00:49:14,720
That's the aliphatic.

1128
00:49:14,720 --> 00:49:17,130
That's the hydrocarbons chain.

1129
00:49:17,130 --> 00:49:18,380
And it is hydrophobic.

1130
00:49:20,660 --> 00:49:23,710
The soil on your clothing is
usually some dirt, but it's

1131
00:49:23,710 --> 00:49:25,750
covered by some grease
and oil.

1132
00:49:25,750 --> 00:49:28,750
So if you just soak it in water,
the water can't get at

1133
00:49:28,750 --> 00:49:30,820
the grease and oil.

1134
00:49:30,820 --> 00:49:33,280
So what you do, is you put these
molecules in that are

1135
00:49:33,280 --> 00:49:39,915
very long, and then they've got
this COO ending, right?

1136
00:49:39,915 --> 00:49:41,350
And now what happens?

1137
00:49:41,350 --> 00:49:44,710
This can form hydrogen bonds
to the water, whereas these

1138
00:49:44,710 --> 00:49:50,100
long hydrophobic tails can bond
to the grease and oil.

1139
00:49:50,100 --> 00:49:51,970
And then you put this in the
washing machine, and what's

1140
00:49:51,970 --> 00:49:53,620
the washing machine do?

1141
00:49:53,620 --> 00:49:55,610
Mechanically agitate.

1142
00:49:55,610 --> 00:49:58,540
So you've got these tails,
hydrophobic tails, stabbing

1143
00:49:58,540 --> 00:50:02,600
the grease and oil, bonded to
the water, shake the living

1144
00:50:02,600 --> 00:50:05,710
daylights out of this, and
release the grease and oil,

1145
00:50:05,710 --> 00:50:09,030
which then will release the
soil, rinse the whole thing,

1146
00:50:09,030 --> 00:50:11,330
and you've got clean clothing.

1147
00:50:11,330 --> 00:50:14,510
So it's the bonding here.

1148
00:50:14,510 --> 00:50:17,020
What you've got is an
amphipathic molecule with a

1149
00:50:17,020 --> 00:50:21,360
hydrophobic tail and a
hydrophilic head that allows

1150
00:50:21,360 --> 00:50:22,870
you to do your laundry.

1151
00:50:22,870 --> 00:50:23,130
All right.

1152
00:50:23,130 --> 00:50:23,700
Get out of here.

1153
00:50:23,700 --> 00:50:25,390
We'll see you on Wednesday.