Extension of the coupled reference interaction site model (RISM)/simulation methodology to the determination of relative solvation free energies of biological complexes

COMP 375

Holly Freedman, holly@mercury.hec.utah.edu1, Ly Le, lyle@mercury.hec.utah.edu1, Linh Huynh1, Dmitry Tikhonov, dmitry.tikhonov@gmail.com2, and Thanh N. Truong, truong@chemistry.chem.utah.edu1. (1) Henry Eyring Center for Theoretical Chemistry / Department of Chemistry, University of Utah, 315 S. 1400 E. Rm 2020, Salt Lake City, UT 84112, (2) Institute of Mathematical Problems of Biology RAS, 4 Institutskaja Str, Pushchino, Moscow Region, 142290, Russia
The comparison of free energies of biological systems in solution requires accurate calculation of solvation components. The coupled reference interaction site model/ simulation methodology determines these as a function of the set of all radial distribution functions of solvent atoms about atomic solute sites, these first having been calculated from simulation trajectories; this method has previously been tested on some small molecular systems. We present results of applications to relative solvation free energies of biological systems, including relative free energies of shifted drug-DNA binding modes, and relative free energies of theophylline and analogues to an RNA aptamer.
 

Free Energy Computations in Drug Discovery
9:00 AM-12:40 PM, Thursday, 14 September 2006 Moscone Center -- Room 220/222, Oral

Division of Computers in Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006