Fragmented blind docking: a novel protein–ligand binding prediction protocol. Issue 24 (26th December 2022)

• Record Type: Journal Article
• Authors: Grasso, Gianvito; Di Gregorio, Arianna; Mavkov, Bojan; Piga, Dario; Labate, Giuseppe Falvo D'Urso; Danani, Andrea; Deriu, Marco A.
• Is Part Of: Journal of biomolecular structure & dynamics. Volume 40:Issue 24(2022)
• Page Start: 13472
• Page End: 13481
• Publication Date: 2022-12-26
• Subjects: Blind docking -- molecular docking -- protein–ligand interactions -- virtual screening; Biomolecules -- Periodicals; Molecular structure -- Periodicals; Molecular Biology -- Periodicals; Biomechanics -- Periodicals; 572
• DOI: 10.1080/07391102.2021.1988709
• Languages: English
• ISSNs: 0739-1102

Abstract

Abstract: In the present paper we propose a novel blind docking protocol based on Autodock-Vina. The developed docking protocol can provide binding site identification and binding pose prediction at the same time, by a systematical exploration of the protein volume performed with several preliminary docking calculations. In our opinion, this protocol can be successfully applied during the first steps of the virtual screening pipeline, because it provides binding site identification and binding pose prediction at the same time without visual evaluation of the binding site. After the binding pose prediction, MM/GBSA re-scoring rescoring procedures has been applied to improve the accuracy of the protein–ligand bound state. The FRAD protocol has been tested on 116 protein–ligand complexes of the Heat Shock Protein 90 – alpha, on 176 of Human Immunodeficiency virus protease 1, and on more than 100 protein–ligand system taken from the PDBbind dataset. Overall, the FRAD approach combined to MM/GBSA re-scoring can be considered as a powerful tool to increase the accuracy and efficiency with respect to other standard docking approaches when the ligand-binding site is unknown. Communicated by Ramaswamy H. Sarma