Synergistic approach to improve ``alchemical'' free energy calculation in rugged energy surface
Abstract
The authors present an integrated approach to "alchemical" free energy simulation, which permits efficient calculation of the free energy difference on rugged energy surface. The method is designed to obtain efficient canonical sampling for rapid free energy convergence. The proposal is motivated by the insight that both the exchange efficiency in the presently designed dualtopology alchemical Hamiltonian replica exchange method (HREM), and the confidence of the free energy determination using the overlap histogramming method, depend on the same criterion, viz., the overlaps of the energy difference histograms between all pairs of neighboring states. Hence, integrating these two techniques can produce a joint solution to the problems of the free energy convergence and conformational sampling in the free energy simulations, in which λ parameter plays two roles to simultaneously facilitate the conformational sampling and improve the phase space overlap for the free energy determination. Specifically, in contrast with other alchemical HREM based free energy simulation methods, the dualtopology approach can ensure robust conformational sampling. Due to these features (a synergistic solution to the free energy convergence and canonical sampling, and the improvement of the sampling efficiency with the dualtopology treatment), the present approach, as demonstrated in the model studies of the authors, is highly efficient in obtaining accurate free energy differences, especially for the systems with rough energy landscapes.
 Publication:

Journal of Chemical Physics
 Pub Date:
 April 2007
 DOI:
 10.1063/1.2715950
 arXiv:
 arXiv:physics/0605005
 Bibcode:
 2007JChPh.126n4109M
 Keywords:

 68.35.Md;
 Surface thermodynamics surface energies;
 Physics  Chemical Physics
 EPrint:
 14 pages with 4 figures