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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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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8156896 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT bakandrzej twodecadesof4dqsaradyingartorstagingacomeback |