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Pre-docking filter for protein and ligand 3D structures
Virtual drug screening using protein-ligand docking techniques is a time-consuming process, which requires high computational power for binding affinity calculation. There are millions of chemical compounds available for docking. Eliminating compounds that are unlikely to exhibit high binding affini...
Autores principales: | , , |
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Formato: | Texto |
Lenguaje: | English |
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Biomedical Informatics Publishing Group
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646187/ https://www.ncbi.nlm.nih.gov/pubmed/19255632 |
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author | Wilantho, Alisa Tongsima, Sissades Jenwitheesuk, Ekachai |
author_facet | Wilantho, Alisa Tongsima, Sissades Jenwitheesuk, Ekachai |
author_sort | Wilantho, Alisa |
collection | PubMed |
description | Virtual drug screening using protein-ligand docking techniques is a time-consuming process, which requires high computational power for binding affinity calculation. There are millions of chemical compounds available for docking. Eliminating compounds that are unlikely to exhibit high binding affinity from the screening set should speed-up the virtual drug screening procedure. We performed docking of 6353 ligands against twenty-one protein X-ray crystal structures. The docked ligands were ranked according to their calculated binding affinities, from which the top five hundred and the bottom five hundred were selected. We found that the volume and number of rotatable bonds of the top five hundred docked ligands are similar to those found in the crystal structures and corresponded with the volume of the binding sites. In contrast, the bottom five hundred set contains ligands that are either too large to enter the binding site, or too small to bind with high specificity and affinity to the binding site. A pre-docking filter that takes into account shapes and volumes of the binding sites as well as ligand volumes and flexibilities can filter out low binding affinity ligands from the screening sets. Thus, the virtual drug screening procedure speed is increased. |
format | Text |
id | pubmed-2646187 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Biomedical Informatics Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-26461872009-03-02 Pre-docking filter for protein and ligand 3D structures Wilantho, Alisa Tongsima, Sissades Jenwitheesuk, Ekachai Bioinformation Hypothesis Virtual drug screening using protein-ligand docking techniques is a time-consuming process, which requires high computational power for binding affinity calculation. There are millions of chemical compounds available for docking. Eliminating compounds that are unlikely to exhibit high binding affinity from the screening set should speed-up the virtual drug screening procedure. We performed docking of 6353 ligands against twenty-one protein X-ray crystal structures. The docked ligands were ranked according to their calculated binding affinities, from which the top five hundred and the bottom five hundred were selected. We found that the volume and number of rotatable bonds of the top five hundred docked ligands are similar to those found in the crystal structures and corresponded with the volume of the binding sites. In contrast, the bottom five hundred set contains ligands that are either too large to enter the binding site, or too small to bind with high specificity and affinity to the binding site. A pre-docking filter that takes into account shapes and volumes of the binding sites as well as ligand volumes and flexibilities can filter out low binding affinity ligands from the screening sets. Thus, the virtual drug screening procedure speed is increased. Biomedical Informatics Publishing Group 2008-12-31 /pmc/articles/PMC2646187/ /pubmed/19255632 Text en © 2008 Biomedical Informatics Publishing Group This is an open-access article, which permits unrestricted use, distribution, and reproduction in any medium, for non-commercial purposes, provided the original author and source are credited. |
spellingShingle | Hypothesis Wilantho, Alisa Tongsima, Sissades Jenwitheesuk, Ekachai Pre-docking filter for protein and ligand 3D structures |
title | Pre-docking filter for protein and ligand 3D structures |
title_full | Pre-docking filter for protein and ligand 3D structures |
title_fullStr | Pre-docking filter for protein and ligand 3D structures |
title_full_unstemmed | Pre-docking filter for protein and ligand 3D structures |
title_short | Pre-docking filter for protein and ligand 3D structures |
title_sort | pre-docking filter for protein and ligand 3d structures |
topic | Hypothesis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646187/ https://www.ncbi.nlm.nih.gov/pubmed/19255632 |
work_keys_str_mv | AT wilanthoalisa predockingfilterforproteinandligand3dstructures AT tongsimasissades predockingfilterforproteinandligand3dstructures AT jenwitheesukekachai predockingfilterforproteinandligand3dstructures |