Practical Guidance for Consensus Scoring and Force Field Selection in Protein-Ligand Binding Free Energy Simulations.

ABSTRACT: The advances in ligand binding affinity prediction have been fostered by system generation tools and improved force fields (FFs). CHARMM-GUI Free Energy Calculator provides input and postprocessing scripts for AMBER-TI free energy calculations with various FFs. In this study, we used 12 different FF combinations (ff14SB and ff19SB for protein, GAFF2.2 and OpenFF for ligand, and TIP3P, TIP4PEW, and OPC for water) to calculate relative binding free energies (ΔΔG_bind) for 80 alchemical transformations (among the JACS benchmark set) with different numbers of λ windows (12 or 21) and simulation times (1, 5, or 10 ns). Our results show that 12 λ windows and 5 ns simulation time for each window are sufficient to obtain reliable ΔΔG_bind with 4 independent

SUBMITTER: Zhang H 

PROVIDER: S-EPMC9772090 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature