Journal Article

GPCR-BSD: a database of binding sites of human G-protein coupled receptors under diverse states

Zhou, Han, Bu, Dongbo, Zhou, Liangliang, Liang, Xinmiao, Li, Xiaonong, Liu, Fan, Zhang, Haicang, Yu, Chungong

2024

Overview

G-protein coupled receptors (GPCRs), the largest family of membrane proteins in human body, involve a great variety of biological processes and thus have become highly valuable drug targets. By binding with ligands (e.g., drugs), GPCRs switch between active and inactive conformational states, thereby performing functions such as signal transmission. The changes in binding pockets under different states are important for a better understanding of drug-target interactions. Therefore it is critical, as well as a practical need, to obtain binding sites in human GPCR structures. We report a database (called GPCR-BSD) that collects 127,990 predicted binding sites of 803 GPCRs under active and inactive states (thus 1,606 structures in total). The binding sites were identified from the predicted GPCR structures by executing three geometric-based pocket prediction methods, fpocket, CavityPlus and GHECOM. The server provides query, visualization, and comparison of the predicted binding sites for both GPCR predicted and experimentally determined structures recorded in PDB. We evaluated the identified pockets of 132 experimentally determined human GPCR structures in terms of pocket residue coverage, pocket center distance and redocking accuracy. The evaluation showed that fpocket and CavityPlus methods performed better and successfully predicted orthosteric binding sites in over 60% of the 132 experimentally determined structures. The GPCR Binding Site database is freely accessible at http://121.41.176.252:8021 . This study not only provides a systematic evaluation of the commonly-used fpocket and CavityPlus methods for the first time but also meets the need for binding site information in GPCR studies.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Algorithms / Analysis / Binding site / Binding Sites / Bioinformatics / Biological activity / Biomedical and Life Sciences / Computational Biology/Bioinformatics / Computer Appl. in Life Sciences / Databases, Protein / Datasets / Drug interactions / G protein-coupled receptors / G proteins / G-protein coupled receptor / Humans / Key residue / Life Sciences / Ligands / Membrane proteins / Methods / Microarrays / Performance evaluation / Predictions / Protein Binding / Protein Conformation / Proteins / Receptors / Receptors, G-Protein-Coupled - chemistry / Receptors, G-Protein-Coupled - metabolism / Signal transmission / Simulation methods / State-specific structure / Therapeutic targets