Would you like to inspect the original subtitles? These are the user uploaded subtitles that are being translated:
0
00:00:00,355 --> 00:00:06,430
ERIC S. LANDER: It turns out that one incredibly smart guy, one extremely
1
00:00:06,430 --> 00:00:11,390
smart guy, said, I don't want to think about the complications.
2
00:00:11,390 --> 00:00:13,980
I want to think about the simple bits.
3
00:00:13,980 --> 00:00:16,320
Let's think about the simple bits first.
4
00:00:16,320 --> 00:00:27,740
And so proteins, secondary structure.
5
00:00:27,740 --> 00:00:32,210
He said, I'm not going to solve the whole thing.
6
00:00:32,210 --> 00:00:36,580
But are there any simple rules?
7
00:00:36,580 --> 00:00:41,880
Now this guy was one of the world's best ever, history's best ever
8
00:00:41,880 --> 00:00:44,910
chemists, a guy called Linus Pauling.
9
00:00:44,910 --> 00:00:49,190
Linus Pauling, who some of you may know, amongst other things, he won two
10
00:00:49,190 --> 00:00:54,480
Nobel prizes, one in chemistry and one for peace.
11
00:00:54,480 --> 00:00:57,914
It's interesting, worth looking up Linus Pauling.
12
00:00:57,914 --> 00:01:03,150
Linus Pauling, he was a very intuitive chemist.
13
00:01:03,150 --> 00:01:09,870
In 1948, he was the Eastman professor at Oxford University in England.
14
00:01:09,870 --> 00:01:12,490
And he caught a cold.
15
00:01:12,490 --> 00:01:15,130
And the weather is terrible, often, in England.
16
00:01:15,130 --> 00:01:17,260
I spent three years going to graduate school in England.
17
00:01:17,260 --> 00:01:19,480
And the weather can be pretty bad.
18
00:01:19,480 --> 00:01:21,120
Linus caught a cold.
19
00:01:21,120 --> 00:01:23,590
And Linus was laid up in bed.
20
00:01:23,590 --> 00:01:26,290
And what most people might do, you know, laid up in bed was
21
00:01:26,290 --> 00:01:27,670
not what Linus did.
22
00:01:27,670 --> 00:01:29,520
Linus said, Oh, I'm laid up in bed.
23
00:01:29,520 --> 00:01:31,010
I can't go to the lab.
24
00:01:31,010 --> 00:01:33,700
I'm going to figure out how proteins fold.
25
00:01:33,700 --> 00:01:35,220
[LAUGHTER]
26
00:01:35,220 --> 00:01:39,590
ERIC S. LANDER: And he had at his disposal paper.
27
00:01:39,590 --> 00:01:42,230
And he started doing origami.
28
00:01:42,230 --> 00:01:46,900
He started folding the paper along the ways that the various different-- like
29
00:01:46,900 --> 00:01:48,230
those bonds, I could tell you--
30
00:01:48,230 --> 00:01:50,650
those rotating thises and thats.
31
00:01:50,650 --> 00:01:54,290
He said, can I make any regularities out of this?
32
00:01:54,290 --> 00:01:56,520
And, of course, what he said was, look, I've got a
33
00:01:56,520 --> 00:01:58,060
peptide bond here, right?
34
00:01:58,060 --> 00:01:58,340
Let's see.
35
00:01:58,340 --> 00:02:00,870
I'm just going to jump right into the middle of a protein here.
36
00:02:00,870 --> 00:02:21,330
C, I've got my C alpha, I've got C alpha, C alpha.
37
00:02:26,510 --> 00:02:31,340
He said, I know those side chains are very, very important.
38
00:02:31,340 --> 00:02:33,480
But I'm going to totally forget about them.
39
00:02:33,480 --> 00:02:35,320
I'm not going to care about the side chain.
40
00:02:35,320 --> 00:02:36,940
I'm not going to care about the side chain.
41
00:02:36,940 --> 00:02:38,300
I'm not going to care about the side chain.
42
00:02:38,300 --> 00:02:47,290
I'm going to note that I have all this wonderful hydrogen bonding potential.
43
00:02:47,290 --> 00:02:51,210
I've got those bonds along the backbone of the protein that can make
44
00:02:51,210 --> 00:02:52,730
hydrogen bonds.
45
00:02:52,730 --> 00:02:55,790
So let me utterly ignore the side chains.
46
00:02:55,790 --> 00:03:02,860
And let me ask, with my paper origami, what patterns can I make making
47
00:03:02,860 --> 00:03:08,550
hydrogen bonds of just the peptide of the protein chain here?
48
00:03:08,550 --> 00:03:16,970
And I will not do justice to it, but what he did was he said, you could
49
00:03:16,970 --> 00:03:21,370
kind of make a helical structure.
50
00:03:21,370 --> 00:03:33,520
And in that helical structure, you could have this pointing at this.
51
00:03:33,520 --> 00:03:37,540
I could have my carboxyl and my amino pointing at each other.
52
00:03:37,540 --> 00:03:43,740
And, he said, if I fold my origami just the right way, it can go around
53
00:03:43,740 --> 00:03:52,050
and around and around, such that at every place it's able to
54
00:03:52,050 --> 00:03:55,470
make bonds like that.
55
00:03:55,470 --> 00:03:59,630
And it's able to continue to come down and make bonds, and make bonds.
56
00:03:59,630 --> 00:04:03,750
And you could get a whole bunch of hydrogen bonds from that backbone
57
00:04:03,750 --> 00:04:04,960
going around.
58
00:04:04,960 --> 00:04:06,290
And you get a helix.
59
00:04:06,290 --> 00:04:18,720
And that helix has 3.7 amino acids per turn, per turn of the helix, by just
60
00:04:18,720 --> 00:04:24,680
perfectly lining up the hydrogen bonds that you can have between this
61
00:04:24,680 --> 00:04:29,460
carboxyl and then 3.7 later, this amino.
62
00:04:29,460 --> 00:04:32,360
And then, onward and onward and onward, every one of them making this
63
00:04:32,360 --> 00:04:36,610
beautiful bond, and making these beautiful hydrogen bonds.
64
00:04:36,610 --> 00:04:38,880
This was the sort of thing that pissed people off.
65
00:04:38,880 --> 00:04:44,010
Because Linus Pauling, sitting in bed with the flu, is able to come up with
66
00:04:44,010 --> 00:04:48,740
the fundamentals of protein structure by just thinking about it.
67
00:04:48,740 --> 00:04:53,360
You know, this is amazing and did not necessarily endear him to others who
68
00:04:53,360 --> 00:04:54,870
didn't think of such things.
69
00:04:54,870 --> 00:04:58,730
Linus calls this the alpha helix.
70
00:05:03,450 --> 00:05:10,130
Not to be outdone, he also says, there's another way I could imagine
71
00:05:10,130 --> 00:05:14,020
using all this hydrogen bonding potential.
72
00:05:14,020 --> 00:05:16,860
Kinda suppose there was a chain of--
73
00:05:16,860 --> 00:05:19,470
and I'm just going to draw this very roughly here--
74
00:05:19,470 --> 00:05:23,160
somehow a chain like that.
75
00:05:23,160 --> 00:05:24,120
And I have--
76
00:05:24,120 --> 00:05:28,470
so here's my peptide backbone here, my protein backbone's going along here--
77
00:05:28,470 --> 00:05:43,680
and I could also do it like that and make lots and lots of bonds along a
78
00:05:43,680 --> 00:05:44,420
long chain.
79
00:05:44,420 --> 00:05:52,210
So instead of making a spiral, a helix, I could have two strands, one
80
00:05:52,210 --> 00:05:57,780
strand and another strand, and I could have lots of hydrogen bonds between
81
00:05:57,780 --> 00:06:00,370
the strands.
82
00:06:00,370 --> 00:06:06,060
And in fact, it turns out, you can get the strands going back, and the
83
00:06:06,060 --> 00:06:08,250
strands going back.
84
00:06:08,250 --> 00:06:12,352
And what you can make are beta sheets.
85
00:06:12,352 --> 00:06:14,260
He utterly ignores the amino acids.
86
00:06:14,260 --> 00:06:16,370
Now you know it's wrong to ignore these amino acids.
87
00:06:16,370 --> 00:06:18,200
I've just told you about these cool amino acids.
88
00:06:18,200 --> 00:06:22,010
But it turns out, Linus was kind of smart here.
89
00:06:22,010 --> 00:06:27,190
He said, many times the amino acids won't matter enough, and its
90
00:06:27,190 --> 00:06:30,830
permissive to be able to make an alpha helix.
91
00:06:30,830 --> 00:06:33,860
And some amino acids are pretty fine with being in an alpha helix.
92
00:06:33,860 --> 00:06:36,500
And some amino acids, you know, they're better for,
93
00:06:36,500 --> 00:06:37,840
you know, beta sheets.
94
00:06:37,840 --> 00:06:42,440
And then there's another possibility, which is neither of the above.
95
00:06:42,440 --> 00:06:46,440
Neither of the above is called loops.
96
00:06:49,770 --> 00:06:54,350
And it means stuff, things that aren't easily classified as beautiful
97
00:06:54,350 --> 00:06:57,400
helices, not easily classified as sheets, but kind of
98
00:06:57,400 --> 00:06:59,050
more random-y loops.
99
00:06:59,050 --> 00:07:04,065
And at a first order approximation, you can kind of make cartoons of a
100
00:07:04,065 --> 00:07:08,380
protein, a cartoon of a protein that has either alpha helices in parts of
101
00:07:08,380 --> 00:07:12,020
it, beta sheets in part of it, or loops in part of it.
102
00:07:12,020 --> 00:07:14,780
Let's actually take a look.
103
00:07:14,780 --> 00:07:18,160
Right here, here's our alpha helix.
104
00:07:18,160 --> 00:07:23,970
And the hydrogen bonds are holding it together along a certain length.
105
00:07:23,970 --> 00:07:28,320
Now, one of the amino acids that will not consent to be part of an alpha
106
00:07:28,320 --> 00:07:32,860
helix, is the one amino acid that's not an amino acid.
107
00:07:32,860 --> 00:07:38,140
Remember, I said that kinky thing, proline, has a constraint.
108
00:07:38,140 --> 00:07:43,290
When there's a proline in an alpha helix, it breaks that alpha helix.
109
00:07:43,290 --> 00:07:46,450
It's kinky, OK?
110
00:07:46,450 --> 00:07:48,230
Here's some beta sheet.
111
00:07:48,230 --> 00:07:51,730
We've got hydrogen bonds, hydrogen bonds, and you can get
112
00:07:51,730 --> 00:07:53,730
these marvelous sheets.
113
00:07:53,730 --> 00:07:56,460
Biologists draw this, and chemists draw this in all different ways.
114
00:07:56,460 --> 00:07:59,710
We have these things we tend to call ribbon diagrams.
115
00:07:59,710 --> 00:08:00,850
Here's my ribbon.
116
00:08:00,850 --> 00:08:02,810
And this long sheet here, we just draw it.
117
00:08:02,810 --> 00:08:04,780
And it's kind of a very nice beta sheet, and it's hydrogen
118
00:08:04,780 --> 00:08:05,800
bonding that way.
119
00:08:05,800 --> 00:08:06,680
So what's this part here?
120
00:08:06,680 --> 00:08:09,010
We call this random coil.
121
00:08:09,010 --> 00:08:10,130
They're all a little bit different.
122
00:08:10,130 --> 00:08:12,800
There's some random coil here and some random coil there.
123
00:08:12,800 --> 00:08:15,170
And so we see beta sheet structures.
124
00:08:15,170 --> 00:08:17,640
We see alpha helix structures.
125
00:08:17,640 --> 00:08:19,184
Any questions?
126
00:08:19,184 --> 00:08:19,950
All right.
127
00:08:19,950 --> 00:08:22,710
So this doesn't totally explain all protein folding, because we've got
128
00:08:22,710 --> 00:08:24,370
those amino acids to care about.
129
00:08:24,370 --> 00:08:27,540
But it gets us some very basic descriptions, alpha
130
00:08:27,540 --> 00:08:29,260
helices, beta sheets.
131
00:08:29,260 --> 00:08:31,730
Take a few minutes to think about what you've just heard by
132
00:08:31,730 --> 00:08:32,980
answering this question.
10809
Can't find what you're looking for?
Get subtitles in any language from opensubtitles.com, and translate them here.