Lecture 31: Protein Structure

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OK, let's go. Settle down. The holiday is over. The holiday is over. Yeah, it's back to business. A couple of announcements: tomorrow will be the last of the weekly quizzes, quiz 12 based on homework 12.

Today I will have office hours a little bit earlier: 2:15 to 3:15. This week is the annual meeting of the Materials Research Society. It's meeting in Boston so I'm tied up with some activities associated with that.

As a matter of fact, the Mayor of Boston, Thomas Menino, and has issued a proclamation declaring today, November 29, as Materials Day in Boston. Yeah, it's very important. I wish I could say I had something to do with it, but I don't even vote in the city of Boston.

So it has nothing to do with me. But, I think it's a nice touch of recognition of the importance of materials. The other thing that I wanted to point out is that on Wednesday, there is a special lecture.

A former 3.091 student and former 3.091 TA by the name of Bill Chernikoff, who has been working with the U.S. Department of Transportation for a number of years, and is focused on alternative transportation is going to be in town.

And, late in the day on Wednesday at 4:00 he'll be giving a lecture on the topic of the hydrogen economy, and the materials issues associated with getting automobiles on the road hydrogen powered. I've hinted at some of these dilemmas in 3.091.

Bill has taught 3.091. He knows the content of 3.091, and I'm sure that his lecture will be pitched at a level that's right on for 3.091 students. So, that's going to be at four o'clock in room 3-270.

If you can swing by, I think you'll be pleasantly entertained and informed by Bill's talk. So, I think that's what I wanted to say. But get down to business, and get back to the learning. Last day, we started biochemistry, and we were looking at amino acids.

And, here's the basic structure of amino acids. We have an sp3 hybridized carbon with four bonds. One ends in an amine shown here, the H2N group. The other ends in an acid. Here's a carboxylic acid.

The third one ends in hydrogen. Three of the four terminuses are specified, and the fourth one is this nature's choice. This is the substituent. In principle, anything that's covalently bonded could fit in there.

But, in practice, there are only 20 found in proteins. And, we saw what those were last day. These are chiral molecules. They have a handedness. 19 of the 20, the exception is glycine. Glycine has the simple R group of hydrogen.

So, if you put a hydrogen here and a hydrogen here we have a molecule that's superimposable. And, later in the lecture, we learned how these behave in aqueous solutions. First thing happens: this proton jumps off the carboxylic acid end, and comes over to the amino end, leaving a negative end on the carboxylic acid side, and a positive end on the amino side.

And, so we have something that's a rather strange looking entity. It's net neutral, but it has a positive, and at a negative end we call it a zwitterion. And we saw last day how zwitterions can behave in acid-based situations very dynamically.

And, they try to respond to changes in the environment by either adding protons or consuming protons. And that's what we've shown in this, oh, quiet. So, that's what's shown in this slide here. And, I have put underneath here are the dominant species.

So, you see over on the very, very low pH side that is to say the solutions that are very acidic, rich in protons, the zwitterion tries to take up as much proton as it can. And it ends up being fully protonated.

And that's denoted here by HAH+. And on the other extreme, the zwitterion sheds all of its protons. And, when you go to very, very high pH. In other words, it tries to neutralize the solution by dumping protons into the solution, and ultimately will denude itself of all protons, and that's shown over here.

And, right dead center, we have the isoelectric point. And, at the isoelectric point, that's the pH at which the zwitterion has to neither shed protons or vacuum up protons in order to stabilize the system.

And, notice that it's not seven. In this particular case, this is for glycine. Glycine has an isoelectric point of around six. And, different amino acids have different isoelectric points. And, we can exploit that.

We can exploit that in the laboratory. So, what I wanted to show you was a way to use this concept of isoelectric point in sorting out amino acids from one another using chemical means. Up until now, we've dominantly been sorting things out on a basis of spectral evidence.

I want to show you a cute experiment. If any of you pursue biology, undoubtedly this is going to be one of the first laboratory exercises you are given. So, what the purpose of the exercise is, is to sort proteins.

So, if we have a protein mixture, we have different proteins. So, they're going to be made up of different amino acids. And the different amino acids have different chemistries; we can sort them by dumping into a gel.

So, this is a column. This is a column, or sometimes it's a pair of glass plates containing a gel in a column. And the gel, as you recall from our solution days is a colloidal dispersion. It's a colloidal dispersion of a solid in a liquid.

And, in this case, the gel consists of some form of inert particles to give a firmness. And, the liquid in this case is in an acid-base medium. In this case, the liquid is acid-base medium. But, it has a peculiar characteristic.

Instead of being uniform pH all along the column, the column is constructed so that pH varies continuously from one end of the column to the other. So, the pH is continuously variable along the column.

So, that's the set. And so, with this situation, what we can do is we can introduce a protein mixture into the top of the column. That's the start. Now the next thing is we're going to do something near and dear to my heart is we're going to put some electrodes across here.

Going to put electrodes at both ends of the columns, and I'm going to send those electrodes to a power supply. And, just for argument's sake, let's make the top of the column negative and the bottom of the column positive.

And, let's see, just to give this some more structure, let's say that this high pH is at the top of the column, and low pH is at the bottom of the column. So, it goes from alkaline down to acidic continuously variable.

And, we put in the protein mixture. As soon as the proteins hit this high pH regime, they all start behaving according to this zwitterion reaction. They're going to start deprotonating like crazy.

But, they're going to be charged. And now, I've got a negative end here and a positive end here. So, those that are weakly negative and strongly positive are going to stay in the vicinity of the top.

Those that are strongly negative are going to be repelled by this electrode, and they're going to start making their way down the column. But this is a dynamic situation. It's not as simple as, OK, all the negatives are going to get attracted to the positive electrode because as the ions move down the column, they are changing pH environments.

And, as they change pH environments, they start accumulating protons. And so eventually, they'll get to the point where they are net neutral. And what happens when the zwitterion is net neutral and electric field? There's no net force.

So, the zwitterion stops. So, each zwitterion will stop at its isoelectric point. So, what we can do is let's say we put in a protein mixture consisting of, say, three different proteins just for argument's sake.

So, they will eventually stop at three different positions in the column corresponding to the three different isoelectric points. The purpose of the electric field is simply to get the ball rolling.

But, as they move, the instant chemistry changes. And at some point, they will be net neutral, and that they will stop. And so, now all I can do is open up the column and go in here and grab the gel in this vicinity and it will consist of one of the proteins alone and none of the others.

So, the concept here is isoelectric focusing. The isoelectric focusing is the principal. All right, let's give it a three letter initialization, IEF. And, this process or this technique by which one sorts, a mixture is called gel electrophoresis.

Electrophoresis is simply the movement of particles through an electric field. This doesn't involve electrochemical processing. We are not actually driving reactions on the two electrodes. The two electrodes are simply there to set up an electric field and cause the charge species, net charge species, to move in one direction or another.

So, this is one application of what's up on that chart. So, very nice. OK, enough about amino acids. Let's start making proteins. So, protein synthesis, and this involves linking amino acids. I mentioned this last day.

That's why we studied amino acids, linking amino acids in order to build a macromolecule. OK, now, which type of polymerization is going to be operative here? We've got two choices. We've got addition polymerization or condensation polymerization.

So, when I look at the amino acid structure, I think about addition polymerization. And I quickly come to the realization that is not going to work because I don't have a double bond coming off the central carbon.

I have only single bonds and if we're going to have addition polymerization, we need to break double bonds and propagate. So, addition polymerization is out. We have to use condensation polymerization owing to the lack of double bonds off the central carbon.

That double bond on the carboxylic acid isn't going to help you. You want to link off the central carbon. So, we need condensation polymerization. Condensation polymerization is the synthesis route used by mother nature.

So, let's take a look at how that might work. I'll draw two amino acids. I'm going to draw this notation here, there's one R group. Here's the carboxylic acid end, and then here's another. I'm going to write this little more fully.

That's the positive amino end, carbon, and just to make the point, this is R prime to indicate that it could be a different amino group, or excuse me, a different substituent. All right, so here's the negative end.

And now, what happens is that by addition polymerization, we grab the oxygen off the carboxylic acid end, and we take to the hydrogens off the amino end and emit a water molecule. And now, we have the capability of bonding the nitrogen on the right to the carbon on the left.

And this bond is called the peptide bond between the carbon and nitrogen. And, let's take a look at similarity here. This was shown a couple of days ago. This was condensation polymerization in inanimate matter.

This is a set of nylons. What we see here is we see, you can take this amino end, and there's a carboxylic acid end. Isn't this looking a little bit like what I've just drawn on the board? And, you see this bond here between carbon and nitrogen? That's called the amide bond.

Here's another amide bond. You know those amide bonds? They're identical to the carbon-nitrogen bond in proteins. So, you know with the holidays coming you start to feel that you're really special? Just look at the structure here.

The bonding in your proteins is not a heck of a lot different from the bonding in a nylon sweater. I'm just showing you chemical similarities. You can enjoy it or not. OK, so what's the difference? The difference is that in the case of nylons, the R group is the same.

Or in this case, there's two R groups. You see in the case of nylon 6-10, you have two mer units that repeat. So, you have the six to the left of the amide bond, and the ten carbons to the right of the amide bond, and then it will be six carbons, and ten carbons, and six carbons, and ten carbons, whereas in the case of proteins, you can choose a different amino acid every time.

There's no pattern here. So, that's why the proteins are macromolecules but they are not strictly polymers. They are not strictly polymers because polymers have a repeating mer unit, whereas this one doesn't.

It doesn't have a repeating mer unit. OK, so we have big variety. We can have R, R prime, R double prime, etc., etc. And, to get a sense of the choice here, let's take a look at what the possibilities are.

Here's one that's shown. This is a dipeptide. This is a dipeptide between phenylalanine and aspartic acid. So phenylalanine and aspartic acid, so, we really have four choices. We can take phenylalanine with phenylalanine or aspartic acid with aspartic acid.

There's the peptide bond. So, these are the dipeptides. And, the convention is always to write with the N terminus on the left. The basic is to the left and the acidic is to the right. So, you'll always see people writing the amino group on the left and ending with the carboxylic acid group on the right.

So, here's the dipeptide phenylalanine, phenylalanine. This is aspartic acid, aspartic acid. And then, there's phenylalanine, aspartic acid, and aspartic acid, phenylalanine. And, it these are two.

You would say, well, this is the same, isn't it? No, these are chiral. These are chiral. So, phenylalanine to the left is distinguishable from aspartic acid to the left. So, you have four combinations here, whereas here, this is insulin.

And just to give you a sense that every R group can be different, so, the only difference here is in the choice of R. So, each one of these positions along the backbone has the amino group, the carboxylic acid group, and the hydrogen.

The only thing that's changing is the substituent, and that's what makes this glycine, valine, etc., etc., glutamic acid, blah, blah, blah. And then, over here is carboxylic acid. And, look at this.

Cysteine must have a double bond in it just like nylons. And we can cross-link nylons with what? Sulfur. And what's mother nature use to cross-link two backbones? Sulfur, and on and on and on. And, here's the carboxylic acid end, and over here is the amino end.

And, I note here Emil Fischer, who won the Nobel Prize in 1902, for his work on structure of sugars and ultimately recognizing that amino acids are involved in protein synthesis. So, this is a simple one.

This is insulin. What do you think the mechanical properties of this molecule are? I bet you it's rubbery. I bet you this is rubbery because it's got the sulfur cross-links. How about it? How do you think this is happening? Oh yeah, a few years ago I had another contest before the Internet.

I used to ask people, you know, you could take all of the amino acids, and you could abbreviate them with three letter initializations. And these are the official three letter initializations. So, I said, could you give me the airports? I looked at this one day and I said, this looks like airport codes.

And I said, what would be the airport code of glycine? Well, let's Mount Goldsworthy Airport at Mount Goldsworthy, Australia. A lot of these are in out-of-the-way places like Australia and Texas and stuff like that.

[LAUGHTER] So, here's a whole bunch of others. 19 of the 20 you can get. Glutamic acid, GLU. As recently as I looked, there is no airport that has the three letter initialization GLU. Somebody once gave me GLV because it's Massachusetts Institute of Technology.

I don't know if you've looked at the front of the building. It says Massachusetts Institute of - you ever see that? Look out front when you're coming in the 77. It says Massachusetts. So, the student said, well, what if I made this? Then it becomes Golovin, AK.

I always wondered why they do that because I thought the Romans couldn't make U's, but then it's of technology, so I don't know. That theory, see, data, data, data. You've got a theory, it might work.

But it doesn't necessarily. OK, so now let's look at what the possibilities are here. So, suppose I want to look at the dipeptides. So, if I want to make the dipeptides, if I take two amino acids and I make dipeptides, I've already shown you, I'm going to make four combinations, two squared.

So, I can make four combinations. And these are distinguishable. Now, I know I've got 20 amino acids. So, if I have 20 amino acids to make dipeptides, I've got 20 squared possibilities is 400 combinations distinguishable, 400 different ways of writing pairs of 20 amino acids allowing for chirality.

Left-right is distinguishable. So then, suppose I took 20 amino acids and I made not two peptides but six. So, I'm making hexapeptides. That's six. So, that would then be 20 to the power of six. And, that would give me about 64 million combinations, taking the 20 amino acids as my library and combining in six blocks of six.

Well, I mean, 64 million is getting up there, but a hexapeptide, I mean, that's hardly a macromolecule. Let's choose a number. Let's get a number. How many should we have to make a halfway decent macromolecule? Let's go to 1,000, shall we? So, let's take 20 amino acids, and we're going to write polypeptides where N, the index of polymerization, equals 1,000.

So then, that becomes 20 raised to the power 1,000, which is ten to the power raised 1,300. That's a huge number. That's a huge number. OK, and that's information. That's information. You see, as you look on this slide here, insulin, as I'm going down, suppose I told you that when you write the final exam, I'm not going to allow you to write it in English characters, in Latin.

I'm going to tell you, you have to write it using the amino acids. So, every time you want to write the letter A, you have to write the chemical symbol alanine. And every time you want to write the letter B, you have to write the chemical symbol for aspartic acid.

You are looking at me like I'm crazy. But that's how nature operates. This is an alphabet. That's information. That's how information is coded. It's coded by what? It's coded by this. Everything else is the same.

There's the information. And, that instant sequence is the letters. That's a poem. That's a poem. We can write a lot of information in here, a lot of information. All right, now let's go back and look at structure.

Let's look at structure. I want to investigate the structure of these proteins because they are not just straight chain molecules. So, for protein structure, we're going to look at three different levels.

We're going to look at three levels. The first one is called the primary structure. And, I'm using terms; I'm kind of wafting back and forth between materials science, solid-state chemistry terms, and the terms that the biologists use because I want you to be literate in the biology terminology so that when you go on into your studies in biology you'll know how to recognize what you are being shown again.

So, the primary structure is just what I talked about now. It's governed by the composition. It's governed by the composition of the protein. Well, what's the composition of the protein? It's just this.

It's just the amino acid sequence. OK, so it's the amino acid sequence, which is to say the R sequence. It's just the R groups down the backbone. So, that's the information. R groups down the backbone, secondary structure: again, this is a term that's used by the biologists, secondary.

We would recognize this in terms of packing. In other words, we saw evidence of this in polymers. Polymers, generally large polymers with twisting and turning in the carbon backbone are amorphous.

But when it's possible to do so, the polymer will fold back on itself to maximize bonding. So, that's why it's packing. It's almost as though it's trying to, and I use this term in quotation marks, it's almost trying to crystallize, that is to say, fold back on itself to maximize internal contact.

And, the driving force is to maximize bonding. The driving force is maximize bonding, not the covalent bonding. Covalent bonding is done once the backbone is formed. So, it's secondary bonding. It's to maximize secondary bonding.

But, it's constrained by geometry. And, I want to show you what I'm talking about here. If I draw this, again, I want to redraw this structure over here in the following way. So, this is the central carbon, and in some texts, it's denoted as the alpha carbon to distinguish it from the carbon up on the carboxylic acid.

So, the alpha carbon, a carboxylic acid, is up here. And that's the one that dumps one of the oxygens, you see? So, the peptide bond comes up off of the second carbon and forms over here to the nitrogen.

And, the nitrogen we've been showing as sp3 hybridized. So, it goes over to its alpha. There is a hydrogen over here, and that there is a lone pair. So, that's what we've been showing. And, if I looked at this, I'd say, well, this thing must lie in a plane.

This thing must lie in a plane because that's got an sp2 hybridized bond. And, that's the way it ought to look. But, it turns out, on the basis of spectral evidence, people learned in the 1940s that all six of these elements, all six of these atoms lie in a plane.

Now, how can that be? This is sp3 hybridized, which means these bonds are 109? apart. There's no way the hydrogen and carbon can lie in the same plane as this carbon. And yet, the spectral evidence indicated it.

So, here's the idea. Just again, this is taken from one of the major biology texts. So, here's the alpha carbon with the amino group, the R group, and the hydrogen. And then, we drop off the oxygen here, make the peptide bond, and then this should be one, two, three, and then the fourth, it gives me the lone pair of electrons.

There is a peptide bond. The data show that all six of these lie in the plane. That's vexing. So, here's what was proposed in 1951 by Linus Pauling and Robert Corey. They said, well, why not come up with a resonance structure that puts alternately a double bond here as we've drawn it with the carboxylic acid up here and up here, and alternatively a double bond on the peptide.

And so, if you have a double bond resonating back and forth, then you can rationalize that you get all six elements lying in a plane. And, that's important. I've got to show you something. It's 1951, and I played for you Guys and Dolls.

I want you to hear a little passage, just runs around 20 seconds. I used to think that the comment about the chemistry between people, that that was sort of a 60s thing. Listen to this: 1951. [VIDEO BEGINS] So, you see back 50 years ago, people were using chemical analogies in musicals on Broadway to talk about, you know.

And so, I want you to understand that these bonds are very important. So, now let's look at how this constrained structure works. So, now that we know we've got all six of these thanks to resonance, we still have the possibilities I showed you before with that C17H36 molecule.

These bonds on the carbon are free to rotate. So, as long as I keep six in a plane this bond can rotate, that bond can rotate and still keep all six of these in a plane, and all six of these in a plane.

The red one lies in both planes. All right, and what are we trying to do? We're trying to maximize bonds. So, there's weak van der Waals bonds. What's the other possible bond? Look at that. See the hydrogen hanging out over here? See oxygen hanging out over here? If we swing these around just the right way, we could give rise to the possibility of hydrogen bonding.

And, that's a compelling reason to move things in a certain orientation. So, what Pauling and Corey did, not only did they say we can rationalize all six of these in a single plane by the resonant structure; they said once you have that resonant structure, this is the way proteins will set themselves up to get best packing, and that fact to maximize hydrogen bonding.

So, first of all, let's get a little bit of this up on the board. So, what I'm going to do is I'm going to show you that here's the alpha carbon going up to the carboxylic acid side: it's lost the oxygen.

It forms the peptide bond, which we've been drawing as a single bond. And then, it goes over to the alpha carbon on the next molecule. Let's see: one, two, three, and here's the lone pair of electrons.

And, they are saying, this is Pauling and Corey, 1951. And they are saying: let's set that up as a resonant structure with the following. Here's alpha carbon. Make a double bond on the peptide. Hydrogen remains the same.

And now, this oxygen is a single bond. It's now a single bond. The double has now jumped over to here. This is just a single: so, one, two, three. And, this thing is going to give up its electron over to here.

So now, this is almost looking zwitterionic. This is looking zwitterionic. And now, we've got the ability with the rotation to form maximal structures. And they proposed the following. They said that there are two structures that will give us a very high incidence of hydrogen bonding.

And the first one is the alpha structure, which is a helix. So, you maximize hydrogen bonding by turning. And, that's shown here. This is 1951, and now you can see the maximal structure of hydrogen bonding by turning.

This gives rise to the possibility of the hydrogen-oxygen between successive galleries as the backbone turns on itself. So, this is the ball and stick, and this is just the stick model. And you can see this blue ribbon giving you the indication of the turn.

And it's a certain kind of a turn because there's a chirality here. If you have only left-handed enantiomers, it's going to dictate the type of turn on it. Here's taken from another text, the same illustration.

So, it turns out that you go around; you end up with an average of 3.6 residues, what they call residues or pendant groups. So, every 3.6 pendant groups, you come back on yourself. 3.6 pendant groups: you come back on yourself, and this lines up hydrogen on the upper gallery with oxygen on the lower gallery to form a vertical hydrogen oxygen bond.

So, that's the first structure they came up with. There was a second structure. The second structure, I think, is pretty obvious. We saw this with nylons. If you just take adjacent chains and offset them a little bit, you've got pendant hydrogens on one side off the amino group, got pendant hydrogens coming off of here, and you've got pendant oxygens coming off of here.

So, why don't I just put another line above, only instead of putting the nitrogen-hydrogen here I'll put the nitrogen-hydrogen here. And now, the hydrogen sitting here will bond. And, the oxygen, and so on.

So, that's shown here. These are adjacent. And, what we get is, recall, when we draw straight line molecule, it's long-term straight. But short-term, it's zigzagging because of the sp3 hybridization.

And so, the alternate zigzagging gives rise to alternate hydrogen, oxygen, hydrogen, oxygen. And, this gives a structure called a sheet. That's the beta structure. Beta is a sheet. Some people call it a pleated sheet or a corrugated sheet sort of along the lines of these pleated skirts.

All right, so you can see how you get the corrugated structure. Here's another one showing side view. You move up and down, up and down. And, side to side, we have the hydrogen bonds forming, OK? So those are the two structures that they enumerated.

And then, the third structure is simply called random. So, these are the three structures, the three types of packing. We either end up with something that's helical, something that is a sheet, or something that's random.

And, if you open any modern journal from the sciences you will see structures that look like this. Let's look at it carefully. We are going to start here. This is the left end. This is the amino terminus.

All right, so this is showing random, and then all of a sudden we get on to this green zone, and the green zone is beta pleated sheet. And, it's shown as just flat. They don't go into detail and show the little zigzag.

So, all along here the molecule is forming maximum hydrogen bonds in this beta pleated sheet arrangement. And then, it goes into some random coil, beta sheet, random coil, beta sheet. And now, look at this blue zone.

This blue zone is alpha helix. And then, it goes random again over here. It looks like we've got a sulfide linkage along the side here. Finally, boom, there's the carboxylic acid end. And, that's one molecule.

That's one molecule. So, for some stretch, it's just random coil. It's straight line, but it's twisting and turning. For other stretches, it's dominantly alpha helix, and other stretches it's beta sheet.

How do we know which it's going to be? Well, that's going to be determined by the instant choice of R groups. So, that's the secondary structure. So, now let's look at tertiary structure. Tertiary structure is what we know as conformation.

And, conformation is governed by interaction between substituents or between R groups. And so, this cartoon, which is taken from your reading, gives you a pretty good indication of the various types of interactions that can take place.

So, they are indicated one, two, three, four, and we'll just go through them. So, what are we looking at here first of all? What's the secondary structure here? We are looking at a run of random coil.

So, now I'm asking you, why is the random coil, for example, more or less straight here? Why does it undergo a left-hand turn here? And, why does it have this hairpin turn over here? It's not just the whim of the artist.

The side groups are dictating this. So, let's go through and observe what the various interactions are. So, look over on the extreme left there, number one: disulfide linkages. These are covalent bonds.

These are covalent bonds. And, clearly, there are certain R groups, the ones that are shown there involve cysteine. And, cysteine has the CH2, and then there is an SH group. And, the SH group, if I have cysteines at a certain distance down the chain, they can dump the hydrogens on the end and form a sulfur-sulfur linkage.

But, instead of being sulfur-sulfur linkage between two different chains, it's sulfur-sulfur linkage between two different side groups of the same chain. And, once the covalent bond forms, would you think the chances are of this stretch of chain now flexing to the left? It can't.

Those sulfur bonds stabilize the backbone. So, they can't move. So, you can change pH. You can do all sorts of things, change the conformation, by whatever means you wish to try. But, it won't move because this sulfur-sulfur covalent bond is too strong.

So, disulfide linkages, then, are going to cause a certain type of conformation, in this case, to stabilize a straight-line structure. So, cysteine is the R group that is involved. And, it forms a parallel path to the backbone.

And, it acts as a stiffener, if you like, to the backbone and prevents movement. Let's look at block number two. What do you see at block number two? It looks like block number two on the left there is a tyrosine and on the right you have aspartic acid.

And, a tyrosine has a hydroxyl hanging off one side. And aspartic acid has that O terminus. What happens if you've got an H hanging near an O? There's hydrogen bonding capability. When that hydrogen bond forms, it causes the chain to bend.

And, it holds it in place. If there weren't that hydrogen bond, the chain might continue to go from top to bottom. So, this is a second type of interaction between side groups that can cause a stabilization of a certain conformation.

So, hydrogen bonding: in this case we see it's between tyrosine and aspartic acid. And there's a few others that have the capability of forming hydrogen bonds. Let's go over to number three. What do we see at number three? We see aspartic acid with its negative end, and we see lysine with its positive end.

Well, if I've got a negative end and I've got a positive end, I have the possibility of electrostatic interactions. So, block three shows electrostatic interactions. And, in the cartoon, you're seeing aspartic acid and lysine.

But there are other combinations, because we saw last day there is a short list of R groups that are positively charged, and R groups that are negatively charged. And, when those end up hanging off the side, they can give rise to either attractive forces or repulsive force.

If we have a bunch of positively charged units next to one another, they will exert a repulsive force and cause the chain to bend the other way. It'll be mutual repulsion. And then, the last one, look at that zone in the upper right there, that pocket.

What you notice about all those? All of those are nonpolar R groups. They're all aliphatic nonpolar R groups. And, the nonpolar R groups are not water-soluble. And so, they tend to collect. And so, that chain folds back on itself to form, it's like a little hydrophobic pocket.

So, it keeps the hydrophilic side presented to the water. It's almost like an incipient fat globule. It's immiscible with water, right? So, these are called hydrophobic interactions. And these involve nonpolar R groups.

And, they cluster. They form clusters. And, they form clusters sort of along the lines of phase separation sort of like oil and water. And, this gives rise to what we see here and allows us to explain what kind of situation we have in that kind of a conformation.

OK, I think this is a good place to stop. I don't think I can quite get through the denaturing of proteins. So, I'd rather not rush through it. So, if you could just hold still without rustling too many papers, let's look at an example of where the secondary structure and tertiary structure is important on a daily basis in your life.

I'm going to talk about something very important. I'm going to talk about hair. Hair is protein. So, I'm going to look at two things. First, I'm going to look at blow drying. And then we are going to look at permanent wave.

So, this is the chemistry of what happens when you try to rearrange your hair by blow drying. So, first of all, the upper cartoon shows hair in its normal state. And, each one of us is different because each one of us has a different arrangement of R groups down the protein.

And, that's why some of us have straight hair and some of us have curly hair because the R groups that are up and down the backbone are going to determine whether we form these kinds of structures which ultimately lead to curling or resist curling.

So, whatever it is, there's hydrogen bonds between adjacent hairs. Now, when you get in the shower and you wet your hair, the water, the free water molecules insert themselves. And now, the hydrogen bonds, instead of going from one chain to the next can go from one chain to a terminal water molecule.

And now, those water molecules are free. So, the bonding between adjacent hairs is disrupted. So, you can think of water acting in this instance as a plasticizer. It's allowing the macromolecules to slip over one another very easily.

And then, you rearrange your hair the way you want it. And then you blow-dry. So, what this cartoon is trying to indicate is that this upper protein has now moved to the left with respect to the lower protein during the course of wetting.

We've got the water in here acting as a plasticizer, move the upper protein to the left, and now we blow-dry. When we blow-dry, we remove this water. And now, the hydrogen bonds must form between adjacent strands.

So, that's how you've rearranged. So now, what's a bad hair day? What's a bad hair day? A bad hair day must be a day that's very moist that allows water to get in here and terminate some of these hydrogen bonds and then allow the hair to go its merry way, opposite what you tried to direct earlier in the day.

So, if you look out and you see its bone dry, you are OK. If it's moist, you might have to resort to more extreme means. Weak hydrogen bonds won't do it. So, here's the next level of artillery. So, we're going to go to covalent bonds.

And what's only covalent bond we have that can go from chain to chain? It's a disulfide linkage. Only in this case the disulfide linkage goes from backbone to backbone. So, we've got cysteine groups that have this HS, and we're going to break the H off, and now form sulfur-sulfur bonds.

So, now, this is really, really strong. But even so, it is always the distant pastures look greener. Those of you with straight hair want it curled. Those with curly hair want it straight. And so, here's what people will resort to.

So, whatever it is, here's the adjacent strands with the disulfide linkages here between strands. So, in this case, you add a reducing agent to now insert hydrogens in here and terminate these. So, now you've got terminal.

Now these things are free to move. We had to do some very aggressive chemistry. But water in here isn't going to do the trick because water won't attack the sulfur-sulfur bonds. So, now we've capped the sulfurs with hydrogen.

And now, you put these on some kind of, I don't know these terms. I don't work in the industry so I don't know these terms. But it's some kind of a mandrel or something. You turn this on, right? So, you turn this and get the curl that you want.

And now that you've got the different strands rearranged versus one another, now you have to reform the covalent bonds, and so now there's peroxide. You've heard the term peroxide blonde. So, there's peroxide.

What's it doing? It's oxidizing and reforming these sulfur-sulfur bonds in the new shape. And, this will last for a very, very long time because these are strong covalent bonds. But, even so, I'll show you next day, even these strong covalent bonds can be broken and denatured.

So, this is a very vivid example of how playing with these forms of bonding can lead to changes in conformation. Ultimately what we are doing is we are changing the shape of the protein. OK, we'll see you on Wednesday.

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