Protein Structure (a very, very short intro)

Before I get into more detail about what I'm working on, I thought I'd start by talking a little bit more about proteins and protein folding.


A protein has structure on several different scales.  The primary structure of a protein is just the sequence of amino acids in its polypeptide chain.  (Remember that a protein is made of one or more polypeptides, polymers made of amino acid monomers that are bound together end-to-end to make a long chain.)  The primary structure of a protein is related to the sequence of messenger RNA by the genetic code.  (Remember: DNA goes to mRNA goes to protein--with some notable exceptions that I can talk more about if you want.)  So we can design a protein with any primary sequence that we want by making a gene with the appropriate DNA sequence.


Proteins aren't just strings of amino acids, though.  That would be boring and probably useless.  Instead, proteins fold into complicated three-dimensional structures.  Some of these structures occur again and again in different proteins.  These basic motifs that occur again and again form what is called secondary structure.  There are several different common secondary structures:  

• The alpha helix is a corkscrew-like arrangement of amino acids that forms because of bonding between every fourth amino acid in the sequence.  (Hydrogen bonding to be specific.)
• The beta sheet is a sheet-like arrangement formed by parallel segments of the polypeptide chain.  Beta sheets are formed by another type of hydrogen bonding between amino acids in neighboring chains.
• Other secondary structures:  The alpha helix and beta sheet are probably the most common secondary structure motifs.  Other secondary structures include turns and weirder types of helices like the 3₁₀ helix and the polyproline helix.

No human being (at least no one I know!) can easily predict what secondary structure a protein will be in just by looking at its primary sequence.  However, people have created sophisticated computer programs that predict secondary structure.  Here are some examples.  These programs sometimes work very well, but they aren't foolproof.  Often, the secondary structure of a particular segment is strongly influenced by interactions with other parts of the protein.  A segment of the polypeptide chain that forms an alpha helix in the full protein, for instance, may not form an alpha helix when it is on its own.

And that brings us to tertiary structure.  Tertiary structure is how all of the amino acids in the polypeptide chain are arranged in three dimensions.  The three-dimensional structure of each protein is extremely important for determining how it will function in the living organism.  Unfortunately, predicting how a protein will fold into its tertiary structure is very, very hard.  However, it is known that the information about how a protein will fold is somehow stored in its primary sequence of amino acids.  People have done classic experiments to show that small proteins can refold on their own after being unfolded by chemical treatment.

A protein typically folds into a well-defined structure determined only by its amino acid sequence.

But how can we predict how it will fold?  This is a huge problem!

So how can we decode the information in the protein's sequence of amino acids to determine how it will fold in three dimensions?  This is a question that scientists are still trying to answer, though most agree that the answer will have something to do with making computer models of protein structure and protein folding.  More on that next time...

Hi from Cambridge!

Hi Peterson students and friends! I've arrived at the University of Cambridge and started working on my new research project, which involves doing computer simulations of protein folding. I'm doing this work with Dr. Robert Best, a fellow in the Cambridge Department of Chemistry. I'd love to tell you all about it and answer any questions you might have.

This will hopefully be the first of a series of posts on my blog about what proteins are, how they fold into complicated 3D structures, and why that is important for life. I apologize in advance if some of what I'm saying is unclear. It will hopefully become clearer as I go on...

But first, here's an animation of one of my first simulations. The coiled tube represents an amino acid chain (a.k.a. polypeptide). You can see three major coiled parts of the chain that pack against each other. These are called alpha helices--more on those later. The structural motif that they form is called a three-helix bundle. The animation shows what happens to the simulated protein if you add to the simulation a strong pulling force between the two ends of the polypeptide chain. The protein quickly comes apart or unfolds. (People have actually done this sort of experiment in real life...but more on that later!)