A Periodic Table of Protein Domains

Johns Hopkins University, Baltimore MD

Investigators

Abstract

This award in the Chemistry of Life Processes (CLP) program of the Chemistry Division and cofunded by Molecular Biophysics in the Division of Molecular and Cellular Bioscience supports work by Professor George D. Rose at Johns Hopkins University to carry out fundamental studies on the theory of protein domains. Proteins are the workhorses of all living systems, responsible for essentially every vital task that takes place in cells. Each protein is a linear chain of amino acid residues that folds into an exquisite three-dimensional structure, one well suited to perform its specialized biological task. The three-dimensional structures are made from a limited number of structural building blocks called domains: the smallest proteins consist of a single domain; larger proteins are composites of multiple domains. Today, the experimentally-determined structure of more than 65,000 proteins is known in atomic detail, and several domain databases have been extracted from these data. However, at present there is no theory of protein domains. The overall goal of this research is to provide such a theory, one based entirely on the physical-chemical properties of polypeptide chains in water, not simply an enumeration from known structures. However, comparison against the known structures would be used to validate the theory. Among the broader impacts, this work would provide a complete "parts list" for experimental structure determination and useful tools for ongoing research in synthetic biology. Beyond these practical applications, a compact theory of protein domains would have a transformative impact on our understanding of protein evolution.