Docking pharmacophore

Step 14 Compile the new hits and convert them in a three-dimensional (3D) format for further studies (docking, pharmacophore search)... 

A VS workflow consists of several sequential filters that are used to discern the molecules that share and those that do not share properties that characterize drugs with a specific bioactivity. In a VS workflow, the molecules that survive a filter are then evaluated by the next filter (whereas the rest are rejected). Thus, a VS workflow is described as a furmel shape to indicate the decreasing number of molecules that are evaluated by the successive filters (Fig. 7.5). Some of the most commonly used filters during VS workflows include ADME/Toxicity analysis, protein-ligand docking, pharmacophore matching and similarity/electrostatic comparison (Fig. 7.5) [99, 120],... 

CPU time. In response to these slow and rigorous calculations, many fast heuristic approaches have been developed that are based on intuitive concepts such as docking [10], matching pharmacophores [19], or linear free energy relationships [20], A disadvantage of many simple heuristic approaches is their susceptibility to generalization error [17], where accuracy of the predictions is limited to the training data. 

Hindle SA, Rarey M, Buning C, Lengauer T. Flexible docking under pharmacophore type constraints. J Comput Aided Mol Des 2002 16 129-49. 

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

Mycobacterium tuberculosis H37Rv Pharmacophore selection of 95 compounds from a database of 15 K, docking to further reduce candidates 4 potent hits [119]... 

In this section, a number of case studies (Table 5) in which different types of VS methods are combined into a hybrid workflow. Often these combine a fast, ligand or pharmacophore-based method with a later docking method. The latter is useful at the inspection stage as it allows the molecule to be reviewed within the context of the protein binding site. A poor binding pose can be an indicator of a poor fit. Furthermore, possible interactions outside the scope of the molecules used to train the ligand-based method can be identified. 

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