Calculation of relative solvation free energies of RNA/drug-binding complexes by the coupled reference interaction site model/molecular dynamics method

COMP 210

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
Better methods are needed to calculate solvation components of relative binding free energies of receptor–ligand interactions. Here this problem is addressed using the coupled reference interaction site model (RISM)/ simulation approach, which allows the RISM solvation free energy expression to be evaluated from the radial distribution functions for solvent atoms about atomic solute sites determined from simulation trajectories. We apply our new methodology for finding solvation free energy to study the thermodynamics of the RNA-drug binding complexes of an RNA aptamer with theophylline and five analogs. The results can be compared with those from the Molecular Mechanics- Poisson-Boltzmann with Solvent Accessible surface area (MM-PBSA) and the Thermodynamics Integration (TI) solvation free energy methods.
 

Poster Session
6:00 PM-8:00 PM, Tuesday, 12 September 2006 Moscone Center -- Hall D, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, 11 September 2006 Moscone Center -- Hall D, Sci-Mix

Division of Computers in Chemistry

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