Computational design of ligand-binding membrane receptors with high selectivity.

ABSTRACT: Accurate modeling and design of protein-ligand interactions have broad applications in cell biology, synthetic biology and drug discovery but remain challenging without experimental protein structures. Here we developed an integrated protein-homology-modeling, ligand-docking protein-design approach that reconstructs protein-ligand binding sites from homolog protein structures in the presence of protein-bound ligand poses to capture conformational selection and induced-fit modes of ligand binding. In structure modeling tests, we blindly predicted, with near-atomic accuracy, ligand conformations bound to G-protein-coupled receptors (GPCRs) that have rarely been identified using traditional approaches. We also quantitatively predicted the binding selectivity of diverse ligands to structurally

SUBMITTER: Feng X 

PROVIDER: S-EPMC5478435 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature