Revisiting MMPBSA by Adoption of MC-Based Surface Area/Volume, ANI-ML Potentials, and Two-Valued Interior Dielectric Constant.

ABSTRACT: Here, we report the accuracy improvements of molecular mechanics Poisson-Boltzmann surface area (MMPBSA) calculations by adoption of ANI-ML potentials in replacement of MM terms, the use of solvent-accessible surface area (SASA) and volume (SAV) values from the Monte Carlo sampling of the probe, and introducing two different interior dielectric constants for electrostatic interactions of protein-ligand (P-L) and polar solvation term in the MMPBSA calculations. Our results show that the Pearson correlation coefficients of MMPBSA-calculated values with respect to experimental binding free energies can be drastically improved from 0.48 to 0.90 by adoption of ANI-ML potentials in replacement of MM energy terms in the equation, referred to as ANI-PBSA. Moreover, we show that the SASA/SAV-combin

SUBMITTER: Akkus E 

PROVIDER: S-EPMC10226125 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature