Fine tuning for success in structure-based virtual screening

Autor:	Claudia Beato, Emilie Pihan, Obdulia Rabal, Constantino Diaz Gonzalez, Martin Kotev
Rok vydání:	2021
Předmět:	Virtual screening Binding Sites business.industry Computer science Process (engineering) Molecular Conformation Proteins Ligands Supercomputer computer.software_genre Automation Computer Science Applications Molecular Docking Simulation Workflow Docking (molecular) Test set Drug Discovery Data mining Physical and Theoretical Chemistry business Protocol (object-oriented programming) computer Algorithms Protein Binding
Zdroj:	Journal of Computer-Aided Molecular Design. 35:1195-1206
ISSN:	1573-4951 0920-654X
DOI:	10.1007/s10822-021-00431-4
Popis:	Structure-based virtual screening plays a significant role in drug-discovery. The method virtually docks millions of compounds from corporate or public libraries into a binding site of a disease-related protein structure, allowing for the selection of a small list of potential ligands for experimental testing. Many algorithms are available for docking and assessing the affinity of compounds for a targeted protein site. The performance of affinity estimation calculations is highly dependent on the size and nature of the site, therefore a rationale for selecting the best protocol is required. To address this issue, we have developed an automated calibration process, implemented in a Knime workflow. It consists of four steps: preparation of a protein test set with structures and models of the target, preparation of a compound test set with target-related ligands and decoys, automatic test of 24 scoring/rescoring protocols for each target structure and model, and graphical display of results. The automation of the process combined with execution on high performance computing resources greatly reduces the duration of the calibration phase, and the test of many combinations of algorithms on various target conformations results in a rational and optimal choice of the best protocol. Here, we present this tool and exemplify its application in setting-up an optimal protocol for SBVS against Retinoid X Receptor alpha.
Databáze:	OpenAIRE
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