Coupling Accelerated Molecular Dynamics Methods with Thermodynamic Integration Simulations

César Augusto F. de Oliveira, Donald Hamelberg, J. Andrew McCammon
2008 Journal of Chemical Theory and Computation  
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-topropane model system. The accuracy of free energy
more » ... ations 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.
doi:10.1021/ct800160q pmid:19461868 pmcid:PMC2646661 fatcat:3zt7gz4rwjgdbpttsls4ygsbdu