Abstract

Summary

Drug discovery targeting G protein-coupled receptors (GPCRs), the largest known class of therapeutic targets, is challenging. To facilitate the rapid discovery and development of GPCR drugs, we built a system, PanGPCR, to predict multiple potential GPCR targets and their expression locations in the tissues, side effects and possible repurposing of GPCR drugs. With PanGPCR, the compound of interest is docked to a library of 36 experimentally determined crystal structures comprising of 46 docking sites for human GPCRs, and a ranked list is generated from the docking studies to assess all GPCRs and their binding affinities. Users can determine a given compound’s GPCR targets and its repurposing potential accordingly. Moreover, potential side effects collected from the SIDER (Side-Effect Resource) database and mapped to 45 tissues and organs are provided by linking predicted off-targets and their expressed sequence tag profiles. With PanGPCR, multiple targets, repurposing potential and side effects can be determined by simply uploading a small ligand.

Availability and implementation

PanGPCR is freely accessible at https://gpcrpanel.cmdm.tw/index.html.

Supplementary information

Supplementary dataSupplementary data are available at Bioinformatics online.

中文翻译：

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PanGPCR：对多个靶标，用途和副作用的预测

摘要

概括

靶向G蛋白偶联受体（GPCR）（已知的最大治疗靶标）的药物发现具有挑战性。为了促进GPCR药物的快速发现和开发，我们构建了PanGPCR系统，以预测多个潜在的GPCR靶标及其在组织中的表达位置，副作用以及GPCR药物的可能用途。使用PanGPCR，将目标化合物停靠到36个实验确定的晶体结构的文库中，该库包含用于人类GPCR的46个停靠位点，并且从停靠研究中生成了一个排序列表，以评估所有GPCR及其结合亲和力。用户可以确定给定化合物的GPCR目标及其相应的潜在用途。而且，通过链接预测的脱靶及其表达的序列标签图谱，可以提供从SIDER（副作用资源）数据库收集并映射到45个组织和器官的潜在副作用。使用PanGPCR，只需上传一个小的配体即可确定多个靶标，再利用的潜力和副作用。

可用性和实施

PanGPCR可从https://gpcrpanel.cmdm.tw/index.html免费访问。

补充资料

补充数据补充数据可从Bioinformatics在线获得。