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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8658842 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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