Inhibitor ranking through QM based chelation calculations for virtual screening of HIV-1 RNase H inhibition.
Quantum mechanical (QM) calculations have been used to predict the binding affinity of a set of ligands towards HIV-1 RT associated RNase H (RNH). The QM based chelation calculations show improved binding affinity prediction for the inhibitors compared to using an empirical scoring function. Further...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4045755?pdf=render |
| _version_ | 1818953563828649984 |
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| author | Vasanthanathan Poongavanam Casper Steinmann Jacob Kongsted |
| author_facet | Vasanthanathan Poongavanam Casper Steinmann Jacob Kongsted |
| author_sort | Vasanthanathan Poongavanam |
| collection | DOAJ |
| description | Quantum mechanical (QM) calculations have been used to predict the binding affinity of a set of ligands towards HIV-1 RT associated RNase H (RNH). The QM based chelation calculations show improved binding affinity prediction for the inhibitors compared to using an empirical scoring function. Furthermore, full protein fragment molecular orbital (FMO) calculations were conducted and subsequently analysed for individual residue stabilization/destabilization energy contributions to the overall binding affinity in order to better understand the true and false predictions. After a successful assessment of the methods based on the use of a training set of molecules, QM based chelation calculations were used as filter in virtual screening of compounds in the ZINC database. By this, we find, compared to regular docking, QM based chelation calculations to significantly reduce the large number of false positives. Thus, the computational models tested in this study could be useful as high throughput filters for searching HIV-1 RNase H active-site molecules in the virtual screening process. |
| first_indexed | 2024-12-20T10:08:16Z |
| format | Article |
| id | doaj.art-78d419b0b1b84d54baa17248c2b8082f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T10:08:16Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-78d419b0b1b84d54baa17248c2b8082f2022-12-21T19:44:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0196e9865910.1371/journal.pone.0098659Inhibitor ranking through QM based chelation calculations for virtual screening of HIV-1 RNase H inhibition.Vasanthanathan PoongavanamCasper SteinmannJacob KongstedQuantum mechanical (QM) calculations have been used to predict the binding affinity of a set of ligands towards HIV-1 RT associated RNase H (RNH). The QM based chelation calculations show improved binding affinity prediction for the inhibitors compared to using an empirical scoring function. Furthermore, full protein fragment molecular orbital (FMO) calculations were conducted and subsequently analysed for individual residue stabilization/destabilization energy contributions to the overall binding affinity in order to better understand the true and false predictions. After a successful assessment of the methods based on the use of a training set of molecules, QM based chelation calculations were used as filter in virtual screening of compounds in the ZINC database. By this, we find, compared to regular docking, QM based chelation calculations to significantly reduce the large number of false positives. Thus, the computational models tested in this study could be useful as high throughput filters for searching HIV-1 RNase H active-site molecules in the virtual screening process.http://europepmc.org/articles/PMC4045755?pdf=render |
| spellingShingle | Vasanthanathan Poongavanam Casper Steinmann Jacob Kongsted Inhibitor ranking through QM based chelation calculations for virtual screening of HIV-1 RNase H inhibition. PLoS ONE |
| title | Inhibitor ranking through QM based chelation calculations for virtual screening of HIV-1 RNase H inhibition. |
| title_full | Inhibitor ranking through QM based chelation calculations for virtual screening of HIV-1 RNase H inhibition. |
| title_fullStr | Inhibitor ranking through QM based chelation calculations for virtual screening of HIV-1 RNase H inhibition. |
| title_full_unstemmed | Inhibitor ranking through QM based chelation calculations for virtual screening of HIV-1 RNase H inhibition. |
| title_short | Inhibitor ranking through QM based chelation calculations for virtual screening of HIV-1 RNase H inhibition. |
| title_sort | inhibitor ranking through qm based chelation calculations for virtual screening of hiv 1 rnase h inhibition |
| url | http://europepmc.org/articles/PMC4045755?pdf=render |
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