ClusPro LigTBM: Automated Template-based Small Molecule Docking. Issue 11 (15th May 2020)

• Record Type: Journal Article
• Authors: Alekseenko, Andrey; Kotelnikov, Sergei; Ignatov, Mikhail; Egbert, Megan; Kholodov, Yaroslav; Vajda, Sandor; Kozakov, Dima
• Is Part Of: Journal of molecular biology. Volume 432:Issue 11(2020)
• Page Start: 3404
• Page End: 3410
• Publication Date: 2020-05-15
• Subjects: protein-ligand docking -- template-based docking -- homology models -- structure refinement; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2019.12.011
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: The template-based approach has been essential for achieving high-quality models in the recent rounds of blind protein-protein docking competition CAPRI (Critical Assessment of Predicted Interactions). However, few such automated methods exist for protein-small molecule docking. In this paper, we present an algorithm for template-based docking of small molecules. It searches for known complexes with ligands that have partial coverage of the target ligand, performs conformational sampling and template-guided energy refinement to produce a variety of possible poses, and then scores the refined poses. The algorithm is available as the automated ClusPro LigTBM server. It allows the user to specify the target protein as a PDB file and the ligand as a SMILES string. The server then searches for templates and uses them for docking, presenting the user with top-scoring poses and their confidence scores. The method is tested on the Astex Diverse benchmark, as well as on the targets from the last round of the D3R (Drug Design Data Resource) Grand Challenge. The server is publicly available as part of the ClusPro docking server suite at https://ligtbm.cluspro.org/ . Graphical abstract: Image 1 Highlights: We present a homology modeling tool to predict protein-ligand interactions. The method performed well in the D3R (Drug Design Data Resource) Grand Challenge. The method has been implemented and is available as the ClusPro LigTBM server. The server was tested on the D3R challenge and the Astex Non-native benchmark set. The protein-ligand templates in the PDB make the method competitive with docking.