Introduction to Protein Folding

Form and function are powerfully related in proteins. One of the keys to understanding how proteins work lies in learning how they fold into particular shapes. Professor Harold Scheraga, a chemist at Cornell University, has dedicated his career to this question. Scheraga has been working with Daniel Ripoll, scientist at the Cornell Theory Center's Parallel Processing Resource for Biomedical Scientists, over the last ten years to simulate protein folding from theory.

Scheraga and his group study the mechanisms of protein folding. They use computers to generate protein molecules from scratch. However, they don't start from a pile of atoms, they don't have to simulate the bonding process. Because they are interested in non-bonding interactions, they start with sequence of the amino acid building blocks and watch as the forces between atoms and among the amino acids change the structure of the molecules.

The researchers study the amino acid alanine as one of their model systems. Taking what they learn from studying this small molecule, they help write the rules that allow us to see inside larger biomolecules, such as genes and enzymes. Their work leads to better tools for biomolecular imaging and rational drug design.

Tortured Trials: Proteins are chains of amino acids assembled inside microscopic factories, or ribosomes, in a living cell. As soon as the chains are released into the cell fluid, they fold into particular shapes (as seen in the images above) and float away quivering with energy, ready for action.

In this computer simulation (QuickTime Movie), a string of alanine molecules struggles to take on the shape that will leave the entire chain settled into a
low energy state. Notice that early on the chain looks like a long spiral, but it's kinked. After lots of gyration, the molecule finally twists into a right-handed spiral, or alpha helix.