Ensemble-based docking: From hit discovery to metabolism and toxicity predictions
| Autor: | Rebecca L. Weir, Jerome Baudry, Sally R. Ellingson, Wilfredo Evangelista, Jason B. Harris, Karan Kapoor, Jeremy C. Smith |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Lead Finder Virtual screening Drug discovery Organic Chemistry Clinical Biochemistry Pharmaceutical Science Computational biology Biology Bioinformatics Biochemistry Article Molecular Docking Simulation 03 medical and health sciences 030104 developmental biology Protein–ligand docking Pharmaceutical Preparations Docking (molecular) Drug Discovery Molecular Medicine Computational Science and Engineering Molecular Biology |
| Zdroj: | Bioorganicmedicinal chemistry. 24(20) |
| ISSN: | 1464-3391 |
| Popis: | This paper describes and illustrates the use of ensemble-based docking, i.e., using a collection of protein structures in docking calculations for hit discovery, the exploration of biochemical pathways and toxicity prediction of drug candidates. We describe the computational engineering work necessary to enable large ensemble docking campaigns on supercomputers. We show examples where ensemble-based docking has significantly increased the number and the diversity of validated drug candidates. Finally, we illustrate how ensemble-based docking can be extended beyond hit discovery and toward providing a structural basis for the prediction of metabolism and off-target binding relevant to pre-clinical and clinical trials. |
| Databáze: | OpenAIRE |
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