Analyzing the robustness of the MM/PBSA free energy calculation method: Application to DNA conformational transitions

COMP 210

Allyn Brice, abrice@clemson.edu and Brian N. Dominy, dominy@clemson.edu. Department of Chemistry, Clemson University, Hunter Chemistry Laboratories, Clemson, SC 29634
The ability to predict conformational equilibria of biomolecules is vital to understanding many important biological processes. The aim of this study is to examine the robustness of the end-point free energy method termed the molecular mechanics Poisson-Boltzmann solvent accessible surface area (MM/PBSA) method. Specifically, applications of MM/PBSA to nucleic acid (NA) systems are explored. MM/PBSA calculations of the free energy difference between A-form and B-form DNA are shown to be in very close agreement with the PMF result determined using an umbrella sampling approach. Further, it is found that the MM/PBSA conformational free energy differences were sensitive to a change from the CHARMM to AMBER force field, however the influence of ionic strength on conformational stability was reproduced very accurately. Finally, a comparison of free energy differences obtained using explicit and implicit solvent models during conformational sampling demonstrates significant differences.
 

Poster Session
6:00 PM-8:00 PM, Tuesday, August 18, 2009 Walter E. Washington Convention Center -- Ballroom A, Poster

Division of Computers in Chemistry

The 238th ACS National Meeting, Washington, DC, August 16-20, 2009