Pulling and Folding Single Molecules
Professor Gaurav Arya
Assistant Professor
Department of NanoEngineering
University of California, San Diego
Wednesday, March 16, 2011
11:00 am – 12:00 pm
Fung Auditorium
Abstract:
Molecular theory and simulations are playing an increasingly important role in nanoengineering. They provide a powerful approach for elucidating molecular mechanisms and guiding the development of new spectroscopy tools for probing single molecules. In this talk, I will discuss ongoing research problems in our group that illustrate both these applications of theoretical modeling.
In the first part of my talk, I will describe our group’s efforts in modeling the 3D folding, dynamics, and regulation of genomic DNA in eukaryotic cells. We have developed a mesoscale model of nucleosome arrays that provides evidence of a polymorphic structure of chromatin; elucidates the role of histone tails, linker histones, and physiological salt in chromatin compaction; and uncovers intriguing features related to the propagation of torsional stresses across nucleosomes. We have also performed detailed atomistic modeling to reveal the molecular mechanism by which the H4 histone tail might mediate strong interactions between nucleosomes and how the acetylation of K16 residue on the tail might disrupt this interaction to trigger chromatin unfolding and subsequent transcriptional activation.
In the second part of my talk, I will describe the development of new theoretical models for analyzing force-extension measurements of single molecule pulling devices like the optical tweezers and AFM. The purpose is to extract from such measurements reliable estimates of the intrinsic energy barriers and transition rates dictating the folding and unfolding of molecules, their conformational transitions, and the stability of molecular complexes. Our models go beyond the current state-of-the-art by accounting for both the finite stiffness of the pulling device and the non-linear stretching of the molecular handles often used to connect the molecule of interest to the pulling device.
Biosketch:
Gaurav Arya is currently an Assistant Professor in the NanoEngineering Department at UCSD. He obtained his Bachelor degree in Chemical Engineering from IIT Bombay in 1998 and his PhD degree in Chemical Engineering from the University of Notre Dame in 2003. He held postdoctoral positions at Princeton University and New York University before joining UCSD in 2007. His research interests are in the areas of statistical mechanics, molecular modeling and simulations, chromatin biophysics, single molecule force spectroscopy, and polymer physics. He has given over 45 invited talks and published over 30 peer-reviewed articles, in leading journals like Annual Review of Biophysics, PNAS, Physical Review Letters, and Advanced Functional Materials.