Defining A Global Map of Functional Group-based 3D Ligand-binding Motifs
- Author:
Yang LIU
1
,
2
;
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
2. 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.
