中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 新药研究国家重点实验室
AlphaFold3 versus experimental structures: assessment of the accuracy in ligand-bound G protein-coupled receptors

文献类型：期刊论文

作者He, Xin-heng1,2; Li, Jun-rui2; Shen, Shi-yi1,2; Xu, H. Eric1,2
刊名ACTA PHARMACOLOGICA SINICA
出版日期2024-12-06
页码12
关键词AlphaFold structure-based drug design artificial intelligence GPCR structural biology
ISSN号1671-4083
DOI10.1038/s41401-024-01429-y
英文摘要G protein-coupled receptors (GPCRs) are critical drug targets involved in numerous physiological processes, yet many of their structures remain unresolved due to inherent flexibility and diverse ligand interactions. This study systematically evaluates the accuracy of AlphaFold3-predicted GPCR structures compared to experimentally determined structures, with a primary focus on ligand-bound states. Our analysis reveals that while AlphaFold3 shows improved performance over AlphaFold2 in predicting overall GPCR backbone architecture, significant discrepancies persist in ligand-binding poses, particularly for ions, peptides, and proteins. Despite advancements, these limitations constrain the utility of AlphaFold3 models in functional studies and structure-based drug design, where high-resolution details of ligand interactions are crucial. We assess the accuracy of predicted structures across various ligand types, quantifying deviations in binding pocket geometries and ligand orientations. Our findings highlight specific challenges in the computational prediction of ligand-bound GPCR structures, emphasizing areas where further refinement is needed. This study provides valuable insights for researchers using AlphaFold3 in GPCR studies, underscores the ongoing necessity for experimental structure determination, and offers direction for improving protein-ligand interaction predictions in future computational models.
WOS关键词GPCR ; DYNAMICS
资助项目National Key R&D Program of China[2022YFC2703105] ; National Natural Science Foundation of China[32130022] ; National Natural Science Foundation of China[82121005] ; CAS Strategic Priority Research Program[XDB37030103] ; Shanghai Municipal Science and Technology Major Project[2019SHZDZX02] ; Shanghai Municipal Science and Technology Major Project (HEX) ; Lingang Laboratory[LG-GG-202204-01]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
WOS记录号WOS:001371403700001
出版者NATURE PUBL GROUP
源URL[http://119.78.100.183/handle/2S10ELR8/314992]  
专题新药研究国家重点实验室
通讯作者Xu, H. Eric
作者单位1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 He, Xin-heng,Li, Jun-rui,Shen, Shi-yi,et al. AlphaFold3 versus experimental structures: assessment of the accuracy in ligand-bound G protein-coupled receptors[J]. ACTA PHARMACOLOGICA SINICA,2024:12.
APA He, Xin-heng,Li, Jun-rui,Shen, Shi-yi,&Xu, H. Eric.(2024).AlphaFold3 versus experimental structures: assessment of the accuracy in ligand-bound G protein-coupled receptors.ACTA PHARMACOLOGICA SINICA,12.
MLA He, Xin-heng,et al."AlphaFold3 versus experimental structures: assessment of the accuracy in ligand-bound G protein-coupled receptors".ACTA PHARMACOLOGICA SINICA (2024):12.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。