Defining A Global Map of Functional Group-based 3D Ligand-binding Motifs
- Author:
Yang LIU
1
;
He WEI
;
Yun YUEHUI
;
Gao YONGXIANG
;
Zhu ZHONGLIANG
;
Teng MAIKUN
;
Liang ZHI
;
Niu LIWEN
Author Information
1. School of Life Sciences,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230026,China;Division of Molecular and Cellular Biophysics,Hefei National Laboratory for Physical Sciences at the Microscale,Hefei 230026,China
- Keywords:
Protein-ligand interaction;
Functional group;
Binding motif;
Computational method;
Drug design
- From:
Genomics, Proteomics & Bioinformatics
2022;20(4):765-779
- CountryChina
- Language:Chinese
-
Abstract:
Uncovering conserved 3D protein-ligand binding patterns on the basis of functional groups(FGs)shared by a variety of small molecules can greatly expand our knowledge of protein-ligand interactions.Despite that conserved binding patterns for a few commonly used FGs have been reported in the literature,large-scale identification and evaluation of FG-based 3D binding motifs are still lacking.Here,we propose a computational method,Automatic FG-based Three-dimensional Motif Extractor(AFTME),for automatic mapping of 3D motifs to different FGs of a specific ligand.Applying our method to 233 naturally-occurring ligands,we define 481 FG-binding motifs that are highly conserved across different ligand-binding pockets.Systematic analysis further reveals four main classes of binding motifs corresponding to distinct sets of FGs.Combinations of FG-binding motifs facilitate the binding of proteins to a wide spectrum of ligands with various binding affinities.Finally,we show that our FG-motif map can be used to nominate FGs that potentially bind to specific drug targets,thus providing useful insights and guidance for rational design of small-molecule drugs.
