Dynamic Docking: A Paradigm Shift in Computational Drug Discovery
Molecular docking is the methodology of choice for studying in silico protein-ligand binding and for prioritizing compounds to discover new lead candidates. Traditional docking simulations suffer from major limitations, mostly related to the static or semi-flexible treatment of ligands and targets....
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2017-11-01
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| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/22/11/2029 |
| _version_ | 1818419818565468160 |
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| author | Dario Gioia Martina Bertazzo Maurizio Recanatini Matteo Masetti Andrea Cavalli |
| author_facet | Dario Gioia Martina Bertazzo Maurizio Recanatini Matteo Masetti Andrea Cavalli |
| author_sort | Dario Gioia |
| collection | DOAJ |
| description | Molecular docking is the methodology of choice for studying in silico protein-ligand binding and for prioritizing compounds to discover new lead candidates. Traditional docking simulations suffer from major limitations, mostly related to the static or semi-flexible treatment of ligands and targets. They also neglect solvation and entropic effects, which strongly limits their predictive power. During the last decade, methods based on full atomistic molecular dynamics (MD) have emerged as a valid alternative for simulating macromolecular complexes. In principle, compared to traditional docking, MD allows the full exploration of drug-target recognition and binding from both the mechanistic and energetic points of view (dynamic docking). Binding and unbinding kinetic constants can also be determined. While dynamic docking is still too computationally expensive to be routinely used in fast-paced drug discovery programs, the advent of faster computing architectures and advanced simulation methodologies are changing this scenario. It is feasible that dynamic docking will replace static docking approaches in the near future, leading to a major paradigm shift in in silico drug discovery. Against this background, we review the key achievements that have paved the way for this progress. |
| first_indexed | 2024-12-14T12:44:37Z |
| format | Article |
| id | doaj.art-b2a1d96fcc534d2fb86ce08fb05b5b35 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-14T12:44:37Z |
| publishDate | 2017-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-b2a1d96fcc534d2fb86ce08fb05b5b352022-12-21T23:00:49ZengMDPI AGMolecules1420-30492017-11-012211202910.3390/molecules22112029molecules22112029Dynamic Docking: A Paradigm Shift in Computational Drug DiscoveryDario Gioia0Martina Bertazzo1Maurizio Recanatini2Matteo Masetti3Andrea Cavalli4Department of Pharmacy and Biotechnology, Alma Mater Studiorum—Universita’ di Bologna, via Belmeloro 6, I-40126 Bologna, ItalyDepartment of Pharmacy and Biotechnology, Alma Mater Studiorum—Universita’ di Bologna, via Belmeloro 6, I-40126 Bologna, ItalyDepartment of Pharmacy and Biotechnology, Alma Mater Studiorum—Universita’ di Bologna, via Belmeloro 6, I-40126 Bologna, ItalyDepartment of Pharmacy and Biotechnology, Alma Mater Studiorum—Universita’ di Bologna, via Belmeloro 6, I-40126 Bologna, ItalyDepartment of Pharmacy and Biotechnology, Alma Mater Studiorum—Universita’ di Bologna, via Belmeloro 6, I-40126 Bologna, ItalyMolecular docking is the methodology of choice for studying in silico protein-ligand binding and for prioritizing compounds to discover new lead candidates. Traditional docking simulations suffer from major limitations, mostly related to the static or semi-flexible treatment of ligands and targets. They also neglect solvation and entropic effects, which strongly limits their predictive power. During the last decade, methods based on full atomistic molecular dynamics (MD) have emerged as a valid alternative for simulating macromolecular complexes. In principle, compared to traditional docking, MD allows the full exploration of drug-target recognition and binding from both the mechanistic and energetic points of view (dynamic docking). Binding and unbinding kinetic constants can also be determined. While dynamic docking is still too computationally expensive to be routinely used in fast-paced drug discovery programs, the advent of faster computing architectures and advanced simulation methodologies are changing this scenario. It is feasible that dynamic docking will replace static docking approaches in the near future, leading to a major paradigm shift in in silico drug discovery. Against this background, we review the key achievements that have paved the way for this progress.https://www.mdpi.com/1420-3049/22/11/2029protein-ligand bindingmolecular dynamicsenhanced samplingbinding kineticsdrug discovery |
| spellingShingle | Dario Gioia Martina Bertazzo Maurizio Recanatini Matteo Masetti Andrea Cavalli Dynamic Docking: A Paradigm Shift in Computational Drug Discovery Molecules protein-ligand binding molecular dynamics enhanced sampling binding kinetics drug discovery |
| title | Dynamic Docking: A Paradigm Shift in Computational Drug Discovery |
| title_full | Dynamic Docking: A Paradigm Shift in Computational Drug Discovery |
| title_fullStr | Dynamic Docking: A Paradigm Shift in Computational Drug Discovery |
| title_full_unstemmed | Dynamic Docking: A Paradigm Shift in Computational Drug Discovery |
| title_short | Dynamic Docking: A Paradigm Shift in Computational Drug Discovery |
| title_sort | dynamic docking a paradigm shift in computational drug discovery |
| topic | protein-ligand binding molecular dynamics enhanced sampling binding kinetics drug discovery |
| url | https://www.mdpi.com/1420-3049/22/11/2029 |
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