DEPARTMENT OF CHEMICAL ENGINEERING SEMINAR

DEPARTMENT OF CHEMICAL ENGINEERING SEMINAR
celebrating 100 YEARS OF SCHOOL OF ENGINEERING

Functional significance of protein dynamics
and relevance to sequence evolution and drug discovery
by Ivet Bahar
School of Medicine, University of Pittsburgh,
Department of Computational and Systems Biology

Date: Nov 7, Wednesday
Time: 16:00
Location: Kare Blok KB 428, Dept. of Chemical Eng., North Campus

Abstract
Biochemical activity and core stability are essential properties of proteins, maintained usually by conserved amino acids. Structural dynamics emerged in recent years as another essential property that defines functional mechanisms as well as the response to substrate- or drug-binding. Yet, the correlation between sequence evolution and structural dynamics is yet to be established. We recently analyzed a set of 34 enzymes with the help of information theory and elastic network models to find that that the structural regions distinguished by coevolutionary propensities serve as substrate recognition sites, whereas residues participating in global hinge centers are often evolutionarily conserved. Our findings highlight the balance between physical adaptability (enabled by structure-encoded motions) and chemical specificity (conferred by correlated amino acid substitutions) as a protein design principle that underlies the selection of a relatively small, but versatile, set of structural modules. Implications with regard to computer-aided drug discovery, and possible strategies against multidrug resistance, will be discussed.

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