Defining a Global Map of Functional Group Based 3D Ligand-binding Motifs
Defining a Global Map of Functional Group Based 3D Ligand-binding Motifs
Abstract Uncovering conserved 3D protein-ligand binding patterns at 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 developed AFTME, an alignment-free method for automatic mapping of 3D motifs to different FGs of a specific ligand through two-dimensional clustering. Applying our method to 233 nature-existing ligands, we defined 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 proteins to bind a wide spectrum of ligands with various binding affinities. Finally, we showed that these general binding patterns are also applicable to target-drug interactions, providing new insights into structure-based drug design.
Yang Liu、Liang Zhi、He Wei、Gao Yongxiang、Yun Yuehui、Teng Maikun、Niu Liwen、Zhu Zhongliang
School of Life Sciences, University of Science and Technology of China||Hefei National Laboratory for Physical Sciences at the Microscale, Division of Molecular and Cellular Biophysics, University of Science and Technology of ChinaSchool of Life Sciences, University of Science and Technology of China||Hefei National Laboratory for Physical Sciences at the Microscale, Division of Molecular and Cellular Biophysics, University of Science and Technology of ChinaSchool of Life Sciences, University of Science and Technology of China||Hefei National Laboratory for Physical Sciences at the Microscale, Division of Molecular and Cellular Biophysics, University of Science and Technology of ChinaSchool of Life Sciences, University of Science and Technology of China||Hefei National Laboratory for Physical Sciences at the Microscale, Division of Molecular and Cellular Biophysics, University of Science and Technology of ChinaSchool of Life Sciences, University of Science and Technology of China||Hefei National Laboratory for Physical Sciences at the Microscale, Division of Molecular and Cellular Biophysics, University of Science and Technology of ChinaSchool of Life Sciences, University of Science and Technology of China||Hefei National Laboratory for Physical Sciences at the Microscale, Division of Molecular and Cellular Biophysics, University of Science and Technology of ChinaSchool of Life Sciences, University of Science and Technology of China||Hefei National Laboratory for Physical Sciences at the Microscale, Division of Molecular and Cellular Biophysics, University of Science and Technology of ChinaSchool of Life Sciences, University of Science and Technology of China||Hefei National Laboratory for Physical Sciences at the Microscale, Division of Molecular and Cellular Biophysics, University of Science and Technology of China
基础医学生物科学研究方法、生物科学研究技术生物化学
Yang Liu,Liang Zhi,He Wei,Gao Yongxiang,Yun Yuehui,Teng Maikun,Niu Liwen,Zhu Zhongliang.Defining a Global Map of Functional Group Based 3D Ligand-binding Motifs[EB/OL].(2025-03-28)[2025-04-28].https://www.biorxiv.org/content/10.1101/2020.09.27.315762.点此复制
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