Albany 2013: Book of Abstracts
June 11-15 2013
©Adenine Press (2012)
Using CG Modeling in Exploring The Role of Dynamical Effects in Catalysis And in Simulating Biological Molecular Machines
Studies of structure function correlation of biological molecules involves in some cases the need to explore long time processes and to sample complex multidimensional landscapes . Here we review advances in such studies , starting by considering the proposal that enzyme catalysis involves dynamical effects ( see Kamerlin et al. 2010 for discussion and analysis ). In order to explore the validity of this dynamical proposal we used our renormalization approach that allows us to simulate the very long time coupling between catalysis and conformational changes. The corresponding simulations have proved that dynamical effects cannot change the rate of the chemical steps in enzymes, as long as the chemistry is the rate-limiting step. The same analysis is then be applied to allosteric transitions and to the control of replication fidelity , reaching the same conclusions. Next we describe the use of the renormalization method and electrostatic based coarse grained (CG) models to simulate the action of various challenging complex systems . It is shown that our CG model produces, for the first time, realistic landscapes for vectrorial process such as the actions of F1 ATPase (Mukherjee and Warshel, 2011) and F0 ATPase (Mukherjee and Warshel, 2012) . It is also shown that such machines are working by exploiting free energy gradients and cannot just use Brownian motions as the vectroial driving force. Finally we outline a recent simulation of the tag of war between staled elongated peptide in the ribosome and the translocon.
Electrostatic Origin of The Mechanochemical Rotary Mechanism And The Catalytic Dwell of F1-ATPase, S. Mukherjee & A. Warshel, Proc. Natl. Acad. Sci. USA ,108, 20550–20555 (2011).
Realistic simulations of the coupling between the protomotive force and the mechanical rotation of the F0-ATPase, S. Mukherjee and A. Warshel, Proc. Natl. Acad. Sci. USA ,109, 14876-14881 (2012).
Department of Chemistry