Molecular dynamics to enhance structure-based virtual screening on cathepsin B
| Autor: | Janez Konc, Izidor Sosič, Samo Lešnik, Mitja Ogrizek, Janko Kos, Stanislav Gobec, Dušanka Janežič, Samo Turk, Bojana Mirković, Milan Hodošček |
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| Rok vydání: | 2015 |
| Předmět: |
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Virtual screening Protein Conformation Chemistry Drug discovery Drug Evaluation Preclinical Computational biology Molecular Dynamics Simulation Molecular Docking Simulation Cathepsin B Computer Science Applications Small Molecule Libraries Molecular dynamics ROC Curve Protein–ligand docking Docking (molecular) Computational chemistry Searching the conformational space for docking Drug Discovery Humans Physical and Theoretical Chemistry |
| Zdroj: | Journal of Computer-Aided Molecular Design. 29:707-712 |
| ISSN: | 1573-4951 0920-654X |
| DOI: | 10.1007/s10822-015-9847-2 |
| Popis: | Molecular dynamics (MD) and molecular docking are commonly used to study molecular interactions in drug discovery. Most docking approaches consider proteins as rigid, which can decrease the accuracy of predicted docked poses. Therefore MD simulations can be used prior to docking to add flexibility to proteins. We evaluated the contribution of using MD together with docking in a docking study on human cathepsin B, a well-studied protein involved in numerous pathological processes. Using CHARMM biomolecular simulation program and AutoDock Vina molecular docking program, we found, that short MD simulations significantly improved molecular docking. Our results, expressed with the area under the receiver operating characteristic curves, show an increase in discriminatory power i.e. the ability to discriminate active from inactive compounds of molecular docking, when docking is performed to selected snapshots from MD simulations. |
| Databáze: | OpenAIRE |
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