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 dual-topology 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 lambda 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 dual-topology 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 dual-topology 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.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.