Multidimensional Global Optimization and Robustness Analysis in the Context of Protein-Ligand Binding.

ABSTRACT: Accuracy of protein-ligand 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 global multidimensional optimization pipeline is developed to find optimal atomic radii specifically for protein-ligand binding calculations in implicit solvent. The computational pipeline has these three key components: (1) a massively parallel implementation of a deterministic global optimization algorithm (VTDIRECT95), (2) an accurate yet reasonably fast generalized Born implicit solvent model (GBNSR6), and (3) a novel robustness metric that helps distinguish between nearly degenerate local minima via a postprocessing step of the optimization. A graph-based "kT<

SUBMITTER: Forouzesh N 

PROVIDER: S-EPMC8594251 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature