An Efficient Implementation of the Nwat-MMGBSA Method to Rescore Docking Results in Medium-Throughput Virtual Screenings
Nwat-MMGBSA is a variant of MM-PB/GBSA based on the inclusion of a number of explicit water molecules that are the closest to the ligand in each frame of a molecular dynamics trajectory. This method demonstrated improved correlations between calculated and experimental binding energies in both prote...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-03-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fchem.2018.00043/full |
| _version_ | 1811193931685167104 |
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| author | Irene Maffucci Xiao Hu Valentina Fumagalli Alessandro Contini |
| author_facet | Irene Maffucci Xiao Hu Valentina Fumagalli Alessandro Contini |
| author_sort | Irene Maffucci |
| collection | DOAJ |
| description | Nwat-MMGBSA is a variant of MM-PB/GBSA based on the inclusion of a number of explicit water molecules that are the closest to the ligand in each frame of a molecular dynamics trajectory. This method demonstrated improved correlations between calculated and experimental binding energies in both protein-protein interactions and ligand-receptor complexes, in comparison to the standard MM-GBSA. A protocol optimization, aimed to maximize efficacy and efficiency, is discussed here considering penicillopepsin, HIV1-protease, and BCL-XL as test cases. Calculations were performed in triplicates on both classic HPC environments and on standard workstations equipped by a GPU card, evidencing no statistical differences in the results. No relevant differences in correlation to experiments were also observed when performing Nwat-MMGBSA calculations on 4 or 1 ns long trajectories. A fully automatic workflow for structure-based virtual screening, performing from library set-up to docking and Nwat-MMGBSA rescoring, has then been developed. The protocol has been tested against no rescoring or standard MM-GBSA rescoring within a retrospective virtual screening of inhibitors of AmpC β-lactamase and of the Rac1-Tiam1 protein-protein interaction. In both cases, Nwat-MMGBSA rescoring provided a statistically significant increase in the ROC AUCs of between 20 and 30%, compared to docking scoring or to standard MM-GBSA rescoring. |
| first_indexed | 2024-04-12T00:17:44Z |
| format | Article |
| id | doaj.art-1cb9495732d14ca0a73c2f3ab4b9b459 |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-04-12T00:17:44Z |
| publishDate | 2018-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-1cb9495732d14ca0a73c2f3ab4b9b4592022-12-22T03:55:48ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462018-03-01610.3389/fchem.2018.00043322405An Efficient Implementation of the Nwat-MMGBSA Method to Rescore Docking Results in Medium-Throughput Virtual ScreeningsIrene MaffucciXiao HuValentina FumagalliAlessandro ContiniNwat-MMGBSA is a variant of MM-PB/GBSA based on the inclusion of a number of explicit water molecules that are the closest to the ligand in each frame of a molecular dynamics trajectory. This method demonstrated improved correlations between calculated and experimental binding energies in both protein-protein interactions and ligand-receptor complexes, in comparison to the standard MM-GBSA. A protocol optimization, aimed to maximize efficacy and efficiency, is discussed here considering penicillopepsin, HIV1-protease, and BCL-XL as test cases. Calculations were performed in triplicates on both classic HPC environments and on standard workstations equipped by a GPU card, evidencing no statistical differences in the results. No relevant differences in correlation to experiments were also observed when performing Nwat-MMGBSA calculations on 4 or 1 ns long trajectories. A fully automatic workflow for structure-based virtual screening, performing from library set-up to docking and Nwat-MMGBSA rescoring, has then been developed. The protocol has been tested against no rescoring or standard MM-GBSA rescoring within a retrospective virtual screening of inhibitors of AmpC β-lactamase and of the Rac1-Tiam1 protein-protein interaction. In both cases, Nwat-MMGBSA rescoring provided a statistically significant increase in the ROC AUCs of between 20 and 30%, compared to docking scoring or to standard MM-GBSA rescoring.http://journal.frontiersin.org/article/10.3389/fchem.2018.00043/fullMM-GBSAexplicit watermolecular dynamicsGPUstructure based virtual screeningprotease |
| spellingShingle | Irene Maffucci Xiao Hu Valentina Fumagalli Alessandro Contini An Efficient Implementation of the Nwat-MMGBSA Method to Rescore Docking Results in Medium-Throughput Virtual Screenings Frontiers in Chemistry MM-GBSA explicit water molecular dynamics GPU structure based virtual screening protease |
| title | An Efficient Implementation of the Nwat-MMGBSA Method to Rescore Docking Results in Medium-Throughput Virtual Screenings |
| title_full | An Efficient Implementation of the Nwat-MMGBSA Method to Rescore Docking Results in Medium-Throughput Virtual Screenings |
| title_fullStr | An Efficient Implementation of the Nwat-MMGBSA Method to Rescore Docking Results in Medium-Throughput Virtual Screenings |
| title_full_unstemmed | An Efficient Implementation of the Nwat-MMGBSA Method to Rescore Docking Results in Medium-Throughput Virtual Screenings |
| title_short | An Efficient Implementation of the Nwat-MMGBSA Method to Rescore Docking Results in Medium-Throughput Virtual Screenings |
| title_sort | efficient implementation of the nwat mmgbsa method to rescore docking results in medium throughput virtual screenings |
| topic | MM-GBSA explicit water molecular dynamics GPU structure based virtual screening protease |
| url | http://journal.frontiersin.org/article/10.3389/fchem.2018.00043/full |
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