Protein Mechanics

Monday, April 25, 2016 - 2:40pm
UT Southwestern
Public Lecture: 

Natural proteins can fold spontaneously into well-defined three-dimensional structures, can carry out complex biochemical properties such as signal transmission, efficient catalysis of chemical reactions, specificity in molecular recognition, and allosteric conformational change. All of this is achieved while also preserving the capacity for rapid adaptive variation in response to fluctuating selection pressures, a central feature of evolving systems. What are the basic principles in the “design” of natural proteins that underlie all of these properties? In previous work, we developed an approach (the statistical coupling analysis or SCA) for globally estimating the pattern of functional interactions between sites on proteins through analysis of the evolutionary divergence of a protein family. This approach indicates a novel decomposition of proteins into sparse groups of co-evolving amino acids that we term “protein sectors”. The sectors comprise physically connected networks in the tertiary structure and can be modular – with different sectors representing different functional properties. Experiments in several protein systems demonstrate the functional and adaptive importance of the sectors and importantly, the SCA information was shown to the necessary and sufficient to design functional artificial members of protein families in the absence of any structural or chemical information. These results support the hypothesis that sectors represent the basic architecture underlying folding, function, and adaptive variation in proteins.  We are now working on two key problems: (1) understanding the physical mechanisms underlying sectors, and (2) defining how the dynamics of the evolutionary process controls the emergence and structural architecture of sectors in proteins

This is a joint Physics / MCB colloquium.