Event

Special Bioengineering Seminar: Divesh Bhatt

Thursday, April 15, 2010
11:00 a.m.
Room 1105, Jeong H. Kim Engineering Building
Professor Sameer Shah
sameer@umd.edu

Path Ensembles for Conformational Transitions in Proteins: Path Heterogeneity, Steady States, and Symmetry

Presented by Divesh Bhatt
University of Pittsburgh School of Medicine

We study conformational transitions in semi-atomistic models of adenylate kinase using weighted ensemble path sampling method. Adenylate kinase shows two dictinct conformations—Open and Closed—and we study transitions in both the directions by generating full path ensembles. The path ensembles show significant heterogeneity, and two distinct pathways are obtained. We find that the qualitative picture of the path ensembles remains unchanged upon inclusion of additional chemical details into our semi-atomistic models. We further present a novel result that establishes the formal conditions necessary to observe symmetry in forward and reverse path ensembles in system under non-equilibrium steady states. We analyze the path ensembles of adenylate kinase in the light of such a symmetry, and investigate the practical conditions that lead to observing the symmetry. A presence of such a symmtery has significant computational implications on systems for which transitions are easier to obtain in one direction—such as ligand unbinding versus binding.

Audience: Graduate  Faculty  Post-Docs