Advances in Potentials of Mean Force Methodology for Organic and Biological Simulations

Orlando Acevedo, Department of Chemistry, Auburn University

Combined quantum and molecular mechanics (QM/MM) simulations have been used to study reaction mechanisms and the origin of enzymatic rate accelerations and selectivity. Speed and accuracy demands have led to the development of enhanced algorithms and a novel potentials of mean force (PMF) method for analytically reproducing free-energy profiles and surfaces with full sampling of solute and solvent coordinates. The methodology has provided excellent results for free-energies of activation for many reactions and has reduced average computation times from ca. 6 months to 3 weeks. The presentation will focus on the development of these methods and will feature recent examples including fatty acid amide hydrolase (FAAH), antibody 4B2, and a singlet oxygen ene reaction.

Oral