Synergistic approach to improve “alchemical” free energy calculation in rugged energy surface

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