Optimal Dielectric Boundary for Binding Free Energy Estimates in the Implicit Solvent.

ABSTRACT: Accuracy of binding free energy calculations utilizing implicit solvent models is critically affected by parameters of the underlying dielectric boundary, specifically, the atomic and water probe radii. Here, a multidimensional optimization pipeline is used to find optimal atomic radii, specifically for binding calculations in the implicit solvent. To reduce overfitting, the optimization target includes separate, weighted contributions from both binding and hydration free energies. The resulting five-parameter radii set, OPT_BIND5D, is evaluated against experiment for binding free energies of 20 host-guest (H-G) systems, unrelated to the types of structures used in the training. The resulting accuracy for this H-G test set (root mean square error of 2.03 kcal/mol, mean signed error of -0.1

SUBMITTER: Forouzesh N 

PROVIDER: S-EPMC11684022 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature