Spatial and temporal coarse-graining in simulations of protein dynamics and complex formation

PHYS 135

Gerhard Hummer, Gerhard.Hummer@nih.gov1, Nicolae-Viorel Buchete, buchete@nih.gov1, Robert B. Best, rbb24@cam.ac.uk2, Wenjun Zheng3, Yng-Gwei Chen1, and Young C. Kim1. (1) Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, (2) Department of Chemistry, Cambridge University, Lensfield Road, Cambridge, United Kingdom, (3) Department of Physics, University at Buffalo, Buffalo, NY 14260
We develop spatial and temporal coarse-graining methods to study large-scale conformational changes in biomolecular systems occurring at the microsecond time scale and beyond. In temporal coarse-graining, master equation models of the conformational dynamics are parameterized with the help of all-atom simulations. Properly validated against the microscopic simulations, the resulting master equations give access to slow conformational transitions such as folding and unfolding while faithfully retaining the equilibrium and dynamic properties of the atomistic protein description. In spatial coarse-graining, we extend the concept of structure-based potentials to molecules with multiple conformational states by constructing coarse-grained energy surfaces that capture the experimentally determined conformers as distinct local minima. This procedure allows us to explore large-scale conformation changes, including transitions that involve partial, local unfolding of proteins. Additional coarse graining, combined with optimized transferable energy functions and accelerated simulation procedures, allows us to study the slow motions in multi-protein complexes involved in membrane-protein trafficking.
 

Multiscale Modeling in Biophysics
8:20 AM-12:20 PM, Monday, April 7, 2008 Morial Convention Center -- Rm. R03, Oral

Division of Physical Chemistry

The 235th ACS National Meeting, New Orleans, LA, April 6-10, 2008