Improvement of accuracy of free-energy landscapes of peptides calculated with generalized Born model by using numerical solutions of Poisson’s equation

We propose an efficient method to improve the accuracy of free-energy landscapes of peptides calculated with the generalized Born (GB) solvation model. A preliminary free-energy landscape is first calculated from a conformation ensemble generated by a multicanonical molecular dynamics simulation with the GB model. Then, it is corrected by replacing the solvation free-energy values of the GB model with those calculated by numerically solving Poisson’s equation. Using this method significantly improved the accuracy of a free-energy landscape of a blocked alanine peptide, Ace-(Ala)3-NMe. The corrected landscape matched well that obtained from a simulation with the explicit solvent model.