Professor of Chemistry and Chemical Biology Eugene I. Shakhnovich and his collaborators, graduate students Eric J. Deeds and Isaac A. Hubner, outline their findings in the scientific journal Proceedings of the National Academy of Sciences. The computer model simulates the lightning-quick process of microscopic protein folding for up to 10 microseconds, or 1,000 times longer than ever before.
“Through a series of dynamic steps,” Shakhnovich explained to The Crimson, the model, which has been in development for over four years, provides a “function for the three-dimensional structure of a protein. In many cases, when we have some insight into the structure of a protein, we have insight into the function of a protein.”
The shape into which a protein folds is determined by the sequence of amino acids that constructs it. The human body has 20 amino acids that can be arranged in any way by the polar forces of water, an abundant compound in cells. Shakhnovich’s model can predict how a certain string of amino acids will fold into a three-dimensional shape with unprecedented accuracy. The team conducted 4,000 simulations that proved to be consistent with experimental results.
The biological function of a protein is then decided by the resulting structure. Through the new computer program, then, Shakhnovich and the scientific community hope to make strides in learning about which amino acids create what proteins to what end.
“In our genomic era, we know many more sequences than structures,” said Shakhnovich, who has worked with proteins for almost 20 years. “When a new protein is discovered, the model gives specific insight into that protein.”
An important practical application is to learn about misfolded proteins, which can lead to disorders, including Alzheimer’s and Parkinson’s diseases. Shakhnovich’s model offers new hope in the fight to treat them.
“We need to know how protein structure changes when a drug binds to it,” Shakhnovich said in reference to drugs that treat such deadly diseases. “The model allows us to address this question. It is a small step, but a step forward.”