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Two Decades of 4D-QSAR: A Dying Art or Staging a Comeback?

A key question confronting computational chemists concerns the preferable ligand geometry that fits complementarily into the receptor pocket. Typically, the postulated ‘bioactive’ 3D ligand conformation is constructed as a ‘sophisticated guess’ (unnecessarily geometry-optimized) mirroring the pharma...

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Autor principal: Bak, Andrzej
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156896/
https://www.ncbi.nlm.nih.gov/pubmed/34069090
http://dx.doi.org/10.3390/ijms22105212
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author Bak, Andrzej
author_facet Bak, Andrzej
author_sort Bak, Andrzej
collection PubMed
description A key question confronting computational chemists concerns the preferable ligand geometry that fits complementarily into the receptor pocket. Typically, the postulated ‘bioactive’ 3D ligand conformation is constructed as a ‘sophisticated guess’ (unnecessarily geometry-optimized) mirroring the pharmacophore hypothesis—sometimes based on an erroneous prerequisite. Hence, 4D-QSAR scheme and its ‘dialects’ have been practically implemented as higher level of model abstraction that allows the examination of the multiple molecular conformation, orientation and protonation representation, respectively. Nearly a quarter of a century has passed since the eminent work of Hopfinger appeared on the stage; therefore the natural question occurs whether 4D-QSAR approach is still appealing to the scientific community? With no intention to be comprehensive, a review of the current state of art in the field of receptor-independent (RI) and receptor-dependent (RD) 4D-QSAR methodology is provided with a brief examination of the ‘mainstream’ algorithms. In fact, a myriad of 4D-QSAR methods have been implemented and applied practically for a diverse range of molecules. It seems that, 4D-QSAR approach has been experiencing a promising renaissance of interests that might be fuelled by the rising power of the graphics processing unit (GPU) clusters applied to full-atom MD-based simulations of the protein-ligand complexes.
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spelling pubmed-81568962021-05-28 Two Decades of 4D-QSAR: A Dying Art or Staging a Comeback? Bak, Andrzej Int J Mol Sci Review A key question confronting computational chemists concerns the preferable ligand geometry that fits complementarily into the receptor pocket. Typically, the postulated ‘bioactive’ 3D ligand conformation is constructed as a ‘sophisticated guess’ (unnecessarily geometry-optimized) mirroring the pharmacophore hypothesis—sometimes based on an erroneous prerequisite. Hence, 4D-QSAR scheme and its ‘dialects’ have been practically implemented as higher level of model abstraction that allows the examination of the multiple molecular conformation, orientation and protonation representation, respectively. Nearly a quarter of a century has passed since the eminent work of Hopfinger appeared on the stage; therefore the natural question occurs whether 4D-QSAR approach is still appealing to the scientific community? With no intention to be comprehensive, a review of the current state of art in the field of receptor-independent (RI) and receptor-dependent (RD) 4D-QSAR methodology is provided with a brief examination of the ‘mainstream’ algorithms. In fact, a myriad of 4D-QSAR methods have been implemented and applied practically for a diverse range of molecules. It seems that, 4D-QSAR approach has been experiencing a promising renaissance of interests that might be fuelled by the rising power of the graphics processing unit (GPU) clusters applied to full-atom MD-based simulations of the protein-ligand complexes. MDPI 2021-05-14 /pmc/articles/PMC8156896/ /pubmed/34069090 http://dx.doi.org/10.3390/ijms22105212 Text en © 2021 by the author. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Bak, Andrzej
Two Decades of 4D-QSAR: A Dying Art or Staging a Comeback?
title Two Decades of 4D-QSAR: A Dying Art or Staging a Comeback?
title_full Two Decades of 4D-QSAR: A Dying Art or Staging a Comeback?
title_fullStr Two Decades of 4D-QSAR: A Dying Art or Staging a Comeback?
title_full_unstemmed Two Decades of 4D-QSAR: A Dying Art or Staging a Comeback?
title_short Two Decades of 4D-QSAR: A Dying Art or Staging a Comeback?
title_sort two decades of 4d-qsar: a dying art or staging a comeback?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156896/
https://www.ncbi.nlm.nih.gov/pubmed/34069090
http://dx.doi.org/10.3390/ijms22105212
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