Past Event: Babuška Forum

Computational Molecular Biophysics: Challenges, Solutions, and Examples

Ron Elber, Professor, CLSB, ICES, UT

Abstract

Molecular Biophysics is a field that studies biological processes at a fundamental level. Muscle contraction, ion transport, signal transduction, and DNA replication are examples of processes that are controlled and driven by molecular machines. Computational modeling of these microscopic machines is of considerable interest as a supplementing option to experimental measurements; an option that provides a comprehensive picture of the equilibrium and kinetics of these systems. A significant challenge for biomolecular simulations is the vast range of spatial and temporal scales of biological processes. In this talk I will focus on the challenge of time scales. The fundamental time step of atomic motions, which is also used in the integration of the equations of motion, is a femtosecond (1E-15s). However, the time scales of many molecular biophysics processes are in the milliseconds and seconds. The last two times require 1E12 and 1E15 integration steps, which is a challenge. Furthermore, the energy landscapes of these systems are rough, making it difficult to apply physics based theory of rare events. Can we conduct meaningful simulations of these systems with such a huge time scale gap? Even with the introduction of special purpose machines, such as Anton [1] statistically converged and direct simulations of experimental observables remain elusive. During the talk I will present a physics based theory and algorithm that make these calculations possible [2,3] . I will also discuss two concrete examples: (i) the work of DNA polymerase that makes copying of genetic material more accurate [4,5], and (ii) the folding and response to load of a component of myosin. Myosin is a muscle protein that converts biological energy (ATP) to mechanical work [6,7]. References 1. D. E. Shaw, M. M. Deneroff, R. O. Dror, J. S. Kuskin, R. H. Larson, J. K. Salmon, C. Young, B. Batson, K. J. Bowers, J. C. Chao, M. P. Eastwood, J. Gagliardo, J. P. Grossman, C. R. Ho, D. J. Ierardi, I. Kolossvary, J. L. Klepeis, T. Layman, C. McLeavey, M. A. Moraes, R. Mueller, E. C. Priest, Y. B. Shan, J. Spengler, M. Theobald, B. Towles and S. C. Wang, Communications of the Acm 51 (7), 91-97 (2008). 2. S. Kirmizialtin and R. Elber, J. Phys. Chem. A 115 (23), 6137-6148 (2011). 3. J. M. Bello-Rivas and R. Elber, Journal of Chemical Physics 142 (9) (2015). 4. S. Kirmizialtin, V. Nguyen, K. A. Johnson and R. Elber, Structure 20 (4), 618-627 (2012). 5. S. Kirmizialtin, K. A. Johnson and R. Elber, Journal of Physical Chemistry B (2015). 6. R. Elber and A. West, Proceedings of the National Academy of Sciences USA 107, 5001-5005 (2010). 7. S. Kreuzer, R. Elber and T.J. Moon, Journal of Physical Chemistry, B, 116,8662-8691(2012)