Virtual ligand based

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

Evers, A., Hessler, G., Matter, H. and Klabunde, T. (2005) Virtual screening of biogenic amine-binding G-protein coupled receptors comparative evaluation of protein- and ligand-based virtual screening protocols. 

The selection of building blocks is based on information derived from, for example, computational chemistry, where potential virtual ligand molecules are modeled to fit the receptor-protein binding site. Combinatorial chemistry commences with a scaffold or framework to which additional groups are added to improve the binding affinity. Compounds are prepared and later screened using HTS. In this way, many compounds are tested within a short time frame to speed up drug discovery. 

Targeted Receptor-Based Virtual Ligand Screening... 

Structural alignments (ligand-based virtual screening) on the basis of a known active compound, molecules that show a good superimposition in shape and physicochemical features are searched for. 

Fig. 4.1 Virtual screening tools can be categorized by the compound data to be screened (compound collection, combinatorial library, chemistry space) and the query type (structure-based, ligand-based, descriptor-based, pharmacophore-based). The output is always a list of compounds together with a score quantifying the fit to the query.

There is no standard procedure for structure- or ligand-based virtual screening. Every prospective application requires understanding and tuning of key parameters. AH... 

Every currently available virtual screening approach in structure- or ligand-based design is heuristic and thus will neither provide any quality guarantee nor an error bound on the obtained results. In every case, the fundamental model describing similarity or... 

New methodologies for ligand-based virtual screening. Current Pharmaceutical Design, 11, 1189-1192. 

Recent examples of successful peptide-ligand based discoveries of drug-like peptidomimetics include the discovery of SST antagonists, or the discovery of non-peptidic antagonists of the recently deorphanized urotensin II receptor at Sanofi-Aventis. ° As illustrated in Fig. 3, Flohr etal. used 3D models of the NMR solution structure of cyclic peptide derivatives of Urotensin II as a template for virtual 3D pharmacophore searches which resulted into non-peptidic candidates for lead optimization. 

Hert J, WiUett P, Wilton DJ, Addin P, Azzaoui K, Jacoby E, Schuffenhauer A. (2005) New Methods for Ligand-Based Virtual Screening Use of Data-Fusion and Machine-Learning Techniques to Enhance the Effectiveness of Similarity Searching. /. Chem. Inf. Model, (in the press). 

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