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Fine tuning for success in structure-based virtual screening.
Pihan, Emilie; Kotev, Martin; Rabal, Obdulia; Beato, Claudia; Diaz Gonzalez, Constantino.
Afiliação
  • Pihan E; Computational Drug Discovery, Evotec (France) SAS, Campus Curie, 195 Route d'Espagne, 31036, Toulouse, France. emilie.pihan@evotec.com.
  • Kotev M; Computational Drug Discovery, Evotec (France) SAS, Campus Curie, 195 Route d'Espagne, 31036, Toulouse, France.
  • Rabal O; Computational Drug Discovery, Evotec (France) SAS, Campus Curie, 195 Route d'Espagne, 31036, Toulouse, France.
  • Beato C; Aptuit (Verona) Srl, an Evotec Company, Via Alessandro Fleming, 4, 37135, Verona, Italy.
  • Diaz Gonzalez C; Computational Drug Discovery, Evotec (France) SAS, Campus Curie, 195 Route d'Espagne, 31036, Toulouse, France.
J Comput Aided Mol Des ; 35(12): 1195-1206, 2021 12.
Article em En | MEDLINE | ID: mdl-34799816
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas / Descoberta de Drogas Tipo de estudo: Diagnostic_studies / Prognostic_studies / Screening_studies Idioma: En Revista: J Comput Aided Mol Des Assunto da revista: BIOLOGIA MOLECULAR / ENGENHARIA BIOMEDICA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: França

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas / Descoberta de Drogas Tipo de estudo: Diagnostic_studies / Prognostic_studies / Screening_studies Idioma: En Revista: J Comput Aided Mol Des Assunto da revista: BIOLOGIA MOLECULAR / ENGENHARIA BIOMEDICA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: França