Virtual workflow

Both ligand- and structure-based methods can be applied in virtual screening. An example of a workflow chart for virtual screening is depicted in Figure 10,4-3. 

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

The result of computational chemistry is some potential drug candidates. These can be synthesized using combinatorial or wet laboratory techniques, and then tested with assays. Screening an array of ligands virtually is cost effective and compresses the discovery timeline. Exhibit 3.10 shows a typical workflow process for virtual screening. 

Bigure 16.5 summarizes our approach to using validated QSAR models for virtual screening as applied to the anticonvulsant dataset. It presents a practical example of the drug discovery workflow that can be generalized for any dataset in which sufficient data to develop reliable QSAR models is available. 

Tropsha, A., Golbraikh, A. (2007) Predictive QSAR modeling workflow, model applicability domains, and virtual screening. Curr PharmaceutDesign 13, 3494-3504. 

Fig. 6.3. Application of predictive QSAR workflow including virtual screening to discover novel HDAC inhibitors.

Each of these metrics gives a different insight into the performance of a screening workflow in retrieving active molecules or discarding inactive ones. Jacobsson et al, for example, used accuracy, sensitivity (which they termed the recall ), yield of actives (termed precision of the active class ) and enrichment to characterize the performance of different structure-based virtual screening workflows [60]. 

Among all the equations, the yield of actives [Eq. (4.3)] and the enrichment [Eq. (4.4)] are probably the most often used the first is the hit rate one that would have if the n selected molecules were tested (again) and the second indicates how many times the virtual screening workflow performs better than a random selection in retrieving active compounds. 

Example of use of a pharmacophore model as a filter in a complete virtual screening workflow (Steindl et al., 2005)... 

To illustrate the power of validated QSAR models as virtual sereening tools we diseuss the examples of studies that resulted in experimentally eonfirmed hits. Sueh studies eould only be performed if there is sufficient data available for a series of tested compounds such that robust validated models could be developing using the workflow described in Figure 10.1. 

Figure 2 Workflows for experimental physical HTS and virtual screening of compound libraries and their combination, for active and inactive componnds, absence and presence of activity are determined with the same degree of reliability. This reliability is an advantage for bnilding SAR models. In addition, the analysis of the dose response curve shapes allows some...

Workflow and Sharing Information within a Virtual Organization... 

Fig. 3.8. A workflow of in silico virtual screening process receptor-based and ligand-based approaches. (See black and white image.)...

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