The compromise of virtual screening and its impact on drug discovery
| Autor: | Maria Kontoyianni, Olivia Slater |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Computer science
Compromise media_common.quotation_subject Scoring criteria Crystallographic data Machine learning computer.software_genre Structure-Activity Relationship 03 medical and health sciences 0302 clinical medicine Drug Discovery Humans Preprocessor Hit selection 030304 developmental biology media_common 0303 health sciences Virtual screening Drug discovery business.industry Molecular Docking Simulation Pharmaceutical Preparations Research Design Docking (molecular) Drug Design 030220 oncology & carcinogenesis Artificial intelligence business computer |
| Zdroj: | Expert Opinion on Drug Discovery. 14:619-637 |
| ISSN: | 1746-045X 1746-0441 |
| Popis: | Introduction: Docking and structure-based virtual screening (VS) have been standard approaches in structure-based design for over two decades. However, our understanding of the limitations, potential, and strength of these techniques has enhanced, raising expectations. Areas covered: Based on a survey of reports in the past five years, we assess whether VS: (1) predicts binding poses in agreement with crystallographic data (when available); (2) is a superior screening tool, as often claimed; (3) is successful in identifying chemical scaffolds that can be starting points for subsequent lead optimization cycles. Data shows that knowledge of the target and its chemotypes in postprocessing lead to viable hits in early drug discovery endeavors. Expert opinion: VS is capable of accurate placements in the pocket for the most part, but does not consistently score screening collections accurately. What matters is capitalization on available resources to get closer to a viable lead or optimizable series. Integration of approaches, subjective hit selection guided by knowledge of the receptor or endogenous ligand, libraries driven by experimental guides, validation studies to identify the best docking/scoring that reproduces experimental findings, constraints regarding receptor-ligand interactions, thoroughly designed methodologies, and predefined cutoff scoring criteria strengthen VS's position in pharmaceutical research. |
| Databáze: | OpenAIRE |
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