Structure-Based Screening Strategies

The accuracy of docking procedures may be evaluated in two ways. First, by detecting known ligand-binding site poses of crystallized complexes, and second, by the enrichment of known active compounds of a mixed library, i.e., enrichment factor. 

The crucial metric for assessing the performance of docking codes is the extent to which a dataset of compounds can be enriched such that only a much smaller subset needs to be prepared and assayed to identify hits or leads. Following Pearhnan and Charifson [36], the enrichment factor can be calculated according to Equation 111. 

The crucial step to judge structure-based approaches is the careful visual inspection of all top scored ligands. An expert should appraise the results with respect to plausible poses of the hits, the presence of key interactions with the binding site residues and different docking solutions for the same ligand. If these and some other requirements are fulfilled, the virtual screening results would have been proved to be extremely valuable. 

Briggs, Uptake of Agrochemicals Pharmaceuticals , Predicting Uptake e(  

Movement of Agrochemicals from Physical Properties, SCI Meeting, 1997. 

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Nonpeptide HFVProtease Inhibitors. Here, more traditional methods and rapid throughput screening of natural products as well as a large array of synthetic compounds from database libraries are pursued. Some compounds deemed to have potential are derived from structure-based design strategies (e.g., complexes with HIV protease). 

Keywords VS, Virtual Screening, Lead discovery, lead, HTS, Pharmacophore-Based, Structure-Based, Fragment-based, Ligand-based, Docking, Scoring, hybrid workflows, VS strategy, Benchmarking VS... 

Eder E, Schiffmann D, Dornbusch K, et al. 1986. Genotoxicity of allyl compounds--A quick screening strategy based on structure-activity relationships and a battery of prescreening tests. Food Chem Toxicol 24 667-673. 

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