FitDock: protein–ligand docking by template fitting

• Published in: Briefings in bioinformatics Vol. 23; no. 3
• Main Authors: Yang, Xiaocong, Liu, Yang, Gan, Jianhong, Xiao, Zhi-Xiong, Cao, Yang
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 13.05.2022; Oxford Publishing Limited (England)
• Subjects: Bioinformatics; Biological activity; CAD; Computer aided design; Crystal structure; Docking; Drug development; Ligands; Molecular modelling; Proteins; protein–ligand docking; molecular alignment; structure prediction
• ISSN: 1467-5463; 1477-4054; 1477-4054
• DOI: 10.1093/bib/bbac087

Abstract Protein–ligand docking is an essential method in computer-aided drug design and structural bioinformatics. It can be used to identify active compounds and reveal molecular mechanisms of biological processes. A successful docking usually requires thorough conformation sampling and scoring, which are computationally expensive and difficult. Recent studies demonstrated that it can be beneficial to docking with the guidance of existing similar co-crystal structures. In this work, we developed a protein–ligand docking method, named FitDock, which fits initial conformation to the given template using a hierarchical multi-feature alignment approach, subsequently explores the possible conformations and finally outputs refined docking poses. In our comprehensive benchmark tests, FitDock showed 40%–60% improvement in terms of docking success rate and an order of magnitude faster over popular docking methods, if template structures exist (> 0.5 ligand similarity). FitDock has been implemented in a user-friendly program, which could serve as a convenient tool for drug design and molecular mechanism exploration. It is now freely available for academic users at http://cao.labshare.cn/fitdock/.