Comparing Fragment Binding Poses Prediction Using HSP90 as a Key Study: When Bound Water Makes the Difference
Fragment-Based Drug Discovery (FBDD) approaches have gained popularity not only in industry but also in academic research institutes. However, the computational prediction of the binding mode adopted by fragment-like molecules within a protein binding site is still a very challenging task. One of th...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/20/4651 |
| _version_ | 1827704481110818816 |
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| author | Giovanni Bolcato Maicol Bissaro Mattia Sturlese Stefano Moro |
| author_facet | Giovanni Bolcato Maicol Bissaro Mattia Sturlese Stefano Moro |
| author_sort | Giovanni Bolcato |
| collection | DOAJ |
| description | Fragment-Based Drug Discovery (FBDD) approaches have gained popularity not only in industry but also in academic research institutes. However, the computational prediction of the binding mode adopted by fragment-like molecules within a protein binding site is still a very challenging task. One of the most crucial aspects of fragment binding is related to the large amounts of bound waters in the targeted binding pocket. The binding affinity of fragments may not be sufficient to displace the bound water molecules. In the present work, we confirmed the importance of the bound water molecules in the correct prediction of the fragment binding mode. Moreover, we investigate whether the use of methods based on explicit solvent molecular dynamics simulations can improve the accuracy of fragment posing. The protein chosen for this study is HSP-90. |
| first_indexed | 2024-03-10T15:41:16Z |
| format | Article |
| id | doaj.art-40f2f212303d4dceb292719ec2af2243 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T15:41:16Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-40f2f212303d4dceb292719ec2af22432023-11-20T16:47:09ZengMDPI AGMolecules1420-30492020-10-012520465110.3390/molecules25204651Comparing Fragment Binding Poses Prediction Using HSP90 as a Key Study: When Bound Water Makes the DifferenceGiovanni Bolcato0Maicol Bissaro1Mattia Sturlese2Stefano Moro3Molecular Modeling Section, Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, ItalyMolecular Modeling Section, Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, ItalyMolecular Modeling Section, Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, ItalyMolecular Modeling Section, Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, ItalyFragment-Based Drug Discovery (FBDD) approaches have gained popularity not only in industry but also in academic research institutes. However, the computational prediction of the binding mode adopted by fragment-like molecules within a protein binding site is still a very challenging task. One of the most crucial aspects of fragment binding is related to the large amounts of bound waters in the targeted binding pocket. The binding affinity of fragments may not be sufficient to displace the bound water molecules. In the present work, we confirmed the importance of the bound water molecules in the correct prediction of the fragment binding mode. Moreover, we investigate whether the use of methods based on explicit solvent molecular dynamics simulations can improve the accuracy of fragment posing. The protein chosen for this study is HSP-90.https://www.mdpi.com/1420-3049/25/20/4651fragment-based drug discoverymolecular dockingmolecular dynamicssupervised molecular dynamicswaterHSP-90 |
| spellingShingle | Giovanni Bolcato Maicol Bissaro Mattia Sturlese Stefano Moro Comparing Fragment Binding Poses Prediction Using HSP90 as a Key Study: When Bound Water Makes the Difference Molecules fragment-based drug discovery molecular docking molecular dynamics supervised molecular dynamics water HSP-90 |
| title | Comparing Fragment Binding Poses Prediction Using HSP90 as a Key Study: When Bound Water Makes the Difference |
| title_full | Comparing Fragment Binding Poses Prediction Using HSP90 as a Key Study: When Bound Water Makes the Difference |
| title_fullStr | Comparing Fragment Binding Poses Prediction Using HSP90 as a Key Study: When Bound Water Makes the Difference |
| title_full_unstemmed | Comparing Fragment Binding Poses Prediction Using HSP90 as a Key Study: When Bound Water Makes the Difference |
| title_short | Comparing Fragment Binding Poses Prediction Using HSP90 as a Key Study: When Bound Water Makes the Difference |
| title_sort | comparing fragment binding poses prediction using hsp90 as a key study when bound water makes the difference |
| topic | fragment-based drug discovery molecular docking molecular dynamics supervised molecular dynamics water HSP-90 |
| url | https://www.mdpi.com/1420-3049/25/20/4651 |
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