PopShift: A thermodynamically sound approach to estimate binding free energies by accounting for ligand-induced population shifts from a ligand-free MSM.

ABSTRACT: Obtaining accurate binding free energies from in silico screens has been a longstanding goal for the computational chemistry community. However, accuracy and computational cost are at odds with one another, limiting the utility of methods that perform this type of calculation. Many methods achieve massive scale by explicitly or implicitly assuming that the target protein adopts a single structure, or undergoes limited fluctuations around that structure, to minimize computational cost. Others simulate each protein-ligand complex of interest, accepting lower throughput in exchange for better predictions of binding affinities. Here, we present the PopShift framework for accounting for the ensemble of structures a protein adopts and their relative probabilities. Protein degrees of freed

SUBMITTER: Smith LG 

PROVIDER: S-EPMC10370083 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature