Coupling accelerated molecular dynamics methods with thermodynamic integration simulations

COMP 226

Cesar Augusto F. de Oliveira,, Howard Hughes Medical Institute and Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, San Diego, CA 92093-0365, Donald Hamelberg,, Department of Chemistry, Georgia State University, Atlanta, GA 30302-4098, and J Andrew McCammon,, Howard Hughes Medical Institute, Department of Chemistry and Biochemistry and Department of Pharmacology, Center for Theoretical Biological Physics, University of California at San Diego, 9500 Gilman Drive, Mail Code 0365, La Jolla, CA 92093-0365.
In this work we propose a straightforward and efficient approach to improve accuracy and convergence of free energy simulations in condensed-phase systems. We also introduce a new accelerated Molecular Dynamics (MD) approach in which molecular conformational transitions are accelerated by lowering the energy barriers while the potential surfaces near the minima are left unchanged. All free energy calculations were performed on the propane-to-propane model system. The accuracy of free energy simulations was significantly improved when sampling of internal degrees of freedom of solute was enhanced. However, accurate and converged results were only achieved when the solvent interactions were taken into account in the accelerated MD approaches. The analysis of the distribution of boost potential along the free energy simulations showed that the new accelerated MD approach samples efficiently both low and high-energy regions of the potential surface. Since this approach also maintains substantial populations in regions near the minima, the statistics are not compromised in the thermodynamic integration calculations, and as a result, the ensemble average can be recovered.

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