title: Matching cavities in g protein-coupled receptors to infer ligand-binding sites.
abstract: To understand the activity and cross reactivity of ligands and G protein-coupled receptors, we take stock of relevant existing receptor mutation, sequence, and structural data to develop a statistically robust and transparent scoring system. Our method evaluates the viability of binding of any ligand for any GPCR sequence of amino acids. This enabled us to explore the binding repertoire of both receptors and ligands, relying solely on correlations between carefully identified receptor features and without requiring any chemical information about ligands. This study suggests that sequence similarity at specific binding pockets can predict relative affinity of ligands; enabling recovery of over 80% of known ligands for a withheld receptor and almost 80% of known receptors for a ligand. The method enables qualitative prediction of ligand binding for all nonredundant human G protein-coupled receptors.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland , St. Lucia, QLD 4072, Australia.
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Madala
authors.forename: David P
authors.initials: DP
authors.lastname: Fairlie
authors.forename: Mikael
authors.initials: M
authors.lastname: Bodén
mesh_terms: D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D006801:Humans; D008024:Ligands; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000235:genetics; D012243:Rhodopsin / Q000737:chemistry
chemical_list: D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D012243:Rhodopsin