How Effectively Can Adaptive Sampling Methods Capture Spontaneous Ligand Binding?

ABSTRACT: Molecular dynamics (MD) simulations that capture the spontaneous binding of drugs and other ligands to their target proteins can reveal a great deal of useful information, but most drug-like ligands bind on time scales longer than those accessible to individual MD simulations. Adaptive sampling methods-in which one performs multiple rounds of simulation, with the initial conditions of each round based on the results of previous rounds-offer a promising potential solution to this problem. No comprehensive analysis of the performance gains from adaptive sampling is available for ligand binding, however, particularly for protein-ligand systems typical of those encountered in drug discovery. Moreover, most previous work presupposes knowledge of the ligand's bound pose. Here we outline existing

SUBMITTER: Betz RM 

PROVIDER: S-EPMC6795214 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature