16
Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Session I Abstracts
Mechanism of Protein Evolution: Conformationaly Dynamics and Allostery
Banu Ozkan
.
Arizona State University, Tempe, AZ, USA.
The first crystal structure was solved in late 1950, which revolutionized our ability to understand
protein function. However, much more revolutionary information came after, when we learned
that proteins dynamically interconvert between conformations in the native state. Indeed, the
critical role of protein dynamics has become well recognized in various biological functions,
including allosteric signaling and protein ligand recognition electron transfer etc. Likewise in
protein evolution, the classical view of the one sequence-one structure-one function paradigm
(the Pauling and Landsteiner proposal) is now being extended to a new view: an ensemble of
conformations in equilibrium that can evolve new functions. Therefore, understanding inherent
structural dynamics are crucial to obtain a more complete picture of protein evolution. A small
local structural change due to a single mutation can lead to a large difference in conformational
dynamics, even at quite distant residues due to allostery. We have recently analyzed
conformational dynamics evolution of different protein families including GFP proteins, beta-
lactamase inhibitors and nuclear receptors, and observed that alteration of conformational
dynamics through allosteric regulations leads to functional changes. Moreover, proteome-wide
conformational dynamics analysis of over 100 human proteins shows a strong correlations
between dynamic profile, and corresponding evolutionary rate of each position. Indeed, the
preservation of dynamic properties of residues in a protein structure is critical for maintaining the
biological function at a proteome scale.
