Expanding automated multiconformer ligand modeling to macrocycles and fragments.

ABSTRACT: Small molecule ligands exhibit a diverse range of conformations in solution. Upon binding to a target protein, this conformational diversity is reduced. However, ligands can retain some degree of conformational flexibility even when bound to a receptor. In the Protein Data Bank, a small number of ligands have been modeled with distinct alternative conformations that are supported by macromolecular X-ray crystallography density maps. However, the vast majority of structural models are fit to a single-ligand conformation, potentially ignoring the underlying conformational heterogeneity present in the sample. We previously developed qFit-ligand to sample diverse ligand conformations and to select a parsimonious ensemble consistent with the density. While this approach indicated that many liga

SUBMITTER: Flowers J 

PROVIDER: S-EPMC12208665 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature