José N. Onuchic
Biological physicist José Onuchic pioneered the study of protein folding, establishing how chains of amino acids fold themselves into the particular structure needed for the protein’s function. In conjunction with collaborators, he discovered the underlying principles governing how information contained in a one-dimensional protein amino-acid sequence determines its resulting three-dimensional structure.
His theoretical framework shows how nature evolved an overall paradigm that guides individual interactions among the amino acids in the folding process through an efficient funnel leading to a unique, stable, native conformation. Evolution has selected mutually supportive amino-acid sequences that cooperatively lead to a structure that minimizes the energy needed, relative to competing shapes. Together, this energy landscape theory and the funnel concept provide a theoretical framework to further explore protein folding and function mechanisms.
Today, with support from Welch, Dr. Onuchic is looking to extend this data-driven approach into two areas. First, he is interested in developing a better understanding of the molecular “motors” that do important work inside the cell, or how proteins interact with each other to perform function. In addition, Dr. Onuchic and his collaborators are developing co-polymer models for chromatin, a much more complex system. Ultimately this will help us unravel how the two-meter long DNA molecule folds itself to fit into a 10-micrometer nucleus, or one million times smaller space – without knotting – critical for successful gene expression.