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Refinement and Rescoring of Virtual Screening Results

High-throughput docking is an established computational screening approach in drug design. This methodology enables a rapid identification of biologically active hit compounds, providing an efficient and cost-effective complement or alternative to experimental high-throughput screenings. However, li...

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Detalles Bibliográficos
Autores principales: Rastelli, Giulio, Pinzi, Luca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637856/
https://www.ncbi.nlm.nih.gov/pubmed/31355188
http://dx.doi.org/10.3389/fchem.2019.00498
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author Rastelli, Giulio
Pinzi, Luca
author_facet Rastelli, Giulio
Pinzi, Luca
author_sort Rastelli, Giulio
collection PubMed
description High-throughput docking is an established computational screening approach in drug design. This methodology enables a rapid identification of biologically active hit compounds, providing an efficient and cost-effective complement or alternative to experimental high-throughput screenings. However, limitations inherent to the methodology make docking results inevitably approximate. Two major Achille's heels include the use of approximated scoring functions and the limited sampling of the ligand-target complexes. Therefore, docking results require careful evaluation and further post-docking analyses. In this article, we will overview our approach to post-docking analysis in virtual screenings. BEAR (Binding Estimation After Refinement) was developed as a post-docking processing tool that refines docking poses by means of molecular dynamics (MD) and then rescores the ligands based on more accurate scoring functions (MM-PB(GB)SA). The tool has been validated and used prospectively in drug discovery applications. Future directions regarding refinement and rescoring in virtual screening are discussed.
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spelling pubmed-66378562019-07-26 Refinement and Rescoring of Virtual Screening Results Rastelli, Giulio Pinzi, Luca Front Chem Chemistry High-throughput docking is an established computational screening approach in drug design. This methodology enables a rapid identification of biologically active hit compounds, providing an efficient and cost-effective complement or alternative to experimental high-throughput screenings. However, limitations inherent to the methodology make docking results inevitably approximate. Two major Achille's heels include the use of approximated scoring functions and the limited sampling of the ligand-target complexes. Therefore, docking results require careful evaluation and further post-docking analyses. In this article, we will overview our approach to post-docking analysis in virtual screenings. BEAR (Binding Estimation After Refinement) was developed as a post-docking processing tool that refines docking poses by means of molecular dynamics (MD) and then rescores the ligands based on more accurate scoring functions (MM-PB(GB)SA). The tool has been validated and used prospectively in drug discovery applications. Future directions regarding refinement and rescoring in virtual screening are discussed. Frontiers Media S.A. 2019-07-11 /pmc/articles/PMC6637856/ /pubmed/31355188 http://dx.doi.org/10.3389/fchem.2019.00498 Text en Copyright © 2019 Rastelli and Pinzi. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Chemistry
Rastelli, Giulio
Pinzi, Luca
Refinement and Rescoring of Virtual Screening Results
title Refinement and Rescoring of Virtual Screening Results
title_full Refinement and Rescoring of Virtual Screening Results
title_fullStr Refinement and Rescoring of Virtual Screening Results
title_full_unstemmed Refinement and Rescoring of Virtual Screening Results
title_short Refinement and Rescoring of Virtual Screening Results
title_sort refinement and rescoring of virtual screening results
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637856/
https://www.ncbi.nlm.nih.gov/pubmed/31355188
http://dx.doi.org/10.3389/fchem.2019.00498
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