Combined Linear Interaction Energy and Alchemical Solvation Free-Energy Approach for Protein-Binding Affinity Computation.

ABSTRACT: Calculating free energies of binding (ΔG_bind) between ligands and their target protein is of major interest to drug discovery and safety, yet it is still associated with several challenges and difficulties. Linear interaction energy (LIE) is an efficient in silico method for ΔG_bind computation. LIE models can be trained and used to directly calculate binding affinities from interaction energies involving ligands in the bound and unbound states only, and LIE can be combined with statistical weighting to calculate ΔG_bind for flexible proteins that may bind their ligands in multiple orientations. Here, we investigate if LIE predictions can be effectively improved by explicitly including the entropy of (de)solvation into our free-energy cal

SUBMITTER: Rifai EA 

PROVIDER: S-EPMC7017367 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature