PLHINT: A knowledge-driven computational approach based on the intermolecular H bond interactions at the protein-ligand interface from docking solutions

Kumar, Sivakumar Prasanth (2018) PLHINT: A knowledge-driven computational approach based on the intermolecular H bond interactions at the protein-ligand interface from docking solutions. In: JOURNAL OF MOLECULAR GRAPHICS & MODELLING, 79 . pp. 194-212.

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Abstract

The tendency of docking scoring functions to generate crystal close conformations of ligands bound to protein structures face limitations in not reproducing the exact crystal intermolecular contacts in dock poses. Intermolecular H bond contacts enumerated at the protein-docked ligand interface can be used to train scoring models and improve virtual screening performance. There is a need to incorporate additional knowledge of protein-ligand H bond contacts in extension to crystal contacts from docking solutions within the reproducibility efficiency of the docking program. A computational approach PLHINT (Protein-ligand H bond interaction pattern) is presented here which extracts intermolecular H bond interactions from native-like docked ligand poses, transform into the scoring scheme and apply over the virtual screening results of database molecules. The basic premise of the PLHINT approach is to score the most observed H bond patterns with the high score to achieve high recovery rates. Tested on ten diverse DUD-E benchmark datasets, the approach has demonstrated better overall performance and ligand enrichment competency over virtual screening results generated by three genetic algorithm-based docking programs viz. AutoDock Vina, FIexAID and PLANTS. Furthermore, the approach has successfully recovered the poor and random virtual screening results with better enrichments. (C) 2017 Elsevier Inc. All rights reserved.

Item Type:	Journal Article
Publication:	JOURNAL OF MOLECULAR GRAPHICS & MODELLING
Additional Information:	Copy right for the article belong to ELSEVIER SCIENCE INC, 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	08 Mar 2018 19:06
Last Modified:	08 Mar 2018 19:06
URI:	http://eprints.iisc.ac.in/id/eprint/59138

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