GPCR-BSD: a database of binding sites of human G-protein coupled receptors under diverse states
Abstract 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 state...
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| Language: | English |
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BMC
2024-11-01
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| Series: | BMC Bioinformatics |
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| Online Access: | https://doi.org/10.1186/s12859-024-05962-9 |
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| author | Fan Liu Han Zhou Xiaonong Li Liangliang Zhou Chungong Yu Haicang Zhang Dongbo Bu Xinmiao Liang |
| author_facet | Fan Liu Han Zhou Xiaonong Li Liangliang Zhou Chungong Yu Haicang Zhang Dongbo Bu Xinmiao Liang |
| author_sort | Fan Liu |
| collection | DOAJ |
| description | Abstract 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 https://gpcrbs.bigdata.jcmsc.cn . 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. |
| format | Article |
| id | doaj-art-19e75286eff4492083c16c7dba165ff2 |
| institution | Kabale University |
| issn | 1471-2105 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Bioinformatics |
| spelling | doaj-art-19e75286eff4492083c16c7dba165ff22024-11-10T12:45:10ZengBMCBMC Bioinformatics1471-21052024-11-0125111610.1186/s12859-024-05962-9GPCR-BSD: a database of binding sites of human G-protein coupled receptors under diverse statesFan Liu0Han Zhou1Xiaonong Li2Liangliang Zhou3Chungong Yu4Haicang Zhang5Dongbo Bu6Xinmiao Liang7University of Chinese Academy of SciencesUniversity of Chinese Academy of SciencesJiangxi Provincial Key Laboratory for Pharmacodynamic Material Basis of Traditional Chinese Medicine, Ganjiang Chinese Medicine Innovation CenterJiangxi Provincial Key Laboratory for Pharmacodynamic Material Basis of Traditional Chinese Medicine, Ganjiang Chinese Medicine Innovation CenterUniversity of Chinese Academy of SciencesUniversity of Chinese Academy of SciencesUniversity of Chinese Academy of SciencesUniversity of Chinese Academy of SciencesAbstract 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 https://gpcrbs.bigdata.jcmsc.cn . 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.https://doi.org/10.1186/s12859-024-05962-9G-protein coupled receptorState-specific structureBinding siteKey residueDatabase |
| spellingShingle | Fan Liu Han Zhou Xiaonong Li Liangliang Zhou Chungong Yu Haicang Zhang Dongbo Bu Xinmiao Liang GPCR-BSD: a database of binding sites of human G-protein coupled receptors under diverse states BMC Bioinformatics G-protein coupled receptor State-specific structure Binding site Key residue Database |
| title | GPCR-BSD: a database of binding sites of human G-protein coupled receptors under diverse states |
| title_full | GPCR-BSD: a database of binding sites of human G-protein coupled receptors under diverse states |
| title_fullStr | GPCR-BSD: a database of binding sites of human G-protein coupled receptors under diverse states |
| title_full_unstemmed | GPCR-BSD: a database of binding sites of human G-protein coupled receptors under diverse states |
| title_short | GPCR-BSD: a database of binding sites of human G-protein coupled receptors under diverse states |
| title_sort | gpcr bsd a database of binding sites of human g protein coupled receptors under diverse states |
| topic | G-protein coupled receptor State-specific structure Binding site Key residue Database |
| url | https://doi.org/10.1186/s12859-024-05962-9 |
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