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Greedy 3-Point Search (G3PS)—A Novel Algorithm for Pharmacophore Alignment

Chemical features of small molecules can be abstracted to 3D pharmacophore models, which are easy to generate, interpret, and adapt by medicinal chemists. Three-dimensional pharmacophores can be used to efficiently match and align molecules according to their chemical feature pattern, which facilita...

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Detalles Bibliográficos
Autores principales: Permann, Christian, Seidel, Thomas, Langer, Thierry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658842/
https://www.ncbi.nlm.nih.gov/pubmed/34885781
http://dx.doi.org/10.3390/molecules26237201
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author Permann, Christian
Seidel, Thomas
Langer, Thierry
author_facet Permann, Christian
Seidel, Thomas
Langer, Thierry
author_sort Permann, Christian
collection PubMed
description Chemical features of small molecules can be abstracted to 3D pharmacophore models, which are easy to generate, interpret, and adapt by medicinal chemists. Three-dimensional pharmacophores can be used to efficiently match and align molecules according to their chemical feature pattern, which facilitates the virtual screening of even large compound databases. Existing alignment methods, used in computational drug discovery and bio-activity prediction, are often not suitable for finding matches between pharmacophores accurately as they purely aim to minimize RMSD or maximize volume overlap, when the actual goal is to match as many features as possible within the positional tolerances of the pharmacophore features. As a consequence, the obtained alignment results are often suboptimal in terms of the number of geometrically matched feature pairs, which increases the false-negative rate, thus negatively affecting the outcome of virtual screening experiments. We addressed this issue by introducing a new alignment algorithm, Greedy 3-Point Search (G3PS), which aims at finding optimal alignments by using a matching-feature-pair maximizing search strategy while at the same time being faster than competing methods.
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spelling pubmed-86588422021-12-10 Greedy 3-Point Search (G3PS)—A Novel Algorithm for Pharmacophore Alignment Permann, Christian Seidel, Thomas Langer, Thierry Molecules Article Chemical features of small molecules can be abstracted to 3D pharmacophore models, which are easy to generate, interpret, and adapt by medicinal chemists. Three-dimensional pharmacophores can be used to efficiently match and align molecules according to their chemical feature pattern, which facilitates the virtual screening of even large compound databases. Existing alignment methods, used in computational drug discovery and bio-activity prediction, are often not suitable for finding matches between pharmacophores accurately as they purely aim to minimize RMSD or maximize volume overlap, when the actual goal is to match as many features as possible within the positional tolerances of the pharmacophore features. As a consequence, the obtained alignment results are often suboptimal in terms of the number of geometrically matched feature pairs, which increases the false-negative rate, thus negatively affecting the outcome of virtual screening experiments. We addressed this issue by introducing a new alignment algorithm, Greedy 3-Point Search (G3PS), which aims at finding optimal alignments by using a matching-feature-pair maximizing search strategy while at the same time being faster than competing methods. MDPI 2021-11-27 /pmc/articles/PMC8658842/ /pubmed/34885781 http://dx.doi.org/10.3390/molecules26237201 Text en © 2021 by the authors. 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 Article
Permann, Christian
Seidel, Thomas
Langer, Thierry
Greedy 3-Point Search (G3PS)—A Novel Algorithm for Pharmacophore Alignment
title Greedy 3-Point Search (G3PS)—A Novel Algorithm for Pharmacophore Alignment
title_full Greedy 3-Point Search (G3PS)—A Novel Algorithm for Pharmacophore Alignment
title_fullStr Greedy 3-Point Search (G3PS)—A Novel Algorithm for Pharmacophore Alignment
title_full_unstemmed Greedy 3-Point Search (G3PS)—A Novel Algorithm for Pharmacophore Alignment
title_short Greedy 3-Point Search (G3PS)—A Novel Algorithm for Pharmacophore Alignment
title_sort greedy 3-point search (g3ps)—a novel algorithm for pharmacophore alignment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658842/
https://www.ncbi.nlm.nih.gov/pubmed/34885781
http://dx.doi.org/10.3390/molecules26237201
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