Virtual screening ligand-based

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. 

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. 

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

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

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). 

Ballester, P. J., Finn, P. W., Richards, W. G. (2009) Ultrafast shape recognition evaluating a new ligand-based virtual screening technology. J Mol Graph Model 27, 836-845. 

Ripphausen P, Nisius B, Bajorath J (2011) State-of-the-art in ligand-based virtual screening. Drug Discov Today 16(9-10) 372-376... 

Geppert H, Vogt M, Bajorath J (2010) Current trends in ligand-based virtual screening molecular representations, data mining methods, new application areas, and performance evaluation. J Chem Inf Model 50(2) 205-216... 

Figure 4.1 Ligand-based virtual screening methods. The figure shows different computational methods for screening compound databases that take either a local or a global view on molecular structure. Molecular similarity methods that operate on molecular descriptors, histogram representations, superposition or (reduced) molecular graphs evaluate molecular structure globally. By contrast, local structural features are explored by substructure and pharmacophore searching or QSAR modeling.

F. L. Stahura and J. Bajorath, New methodologies for ligand-based virtual screening, Curr. Pharm. Des., 2005, 11, 1189. 

Probabilistic Ligand-based Virtual Screening Methods... 

In general, any ligand-based virtual screening method is based on direct or generalized similarity between the screened compound and compounds from the training set. Therefore, if such similarity is absent at all, no reasonable prediction of screened compound s properties can be made by using this training set. 

In the case of ligand based virtual screening, ligands can be compared to each other similarly to the comparison between ligands and a protein structure. 

Ligand based virtual screening has been performed with FLAP on an in-house project at Pfizer, Sandwich Laboratories. For reasons of confidentiality we cannot disclose details of the structures for the project. Both active ligands and receptor structures were available. 

The calculation of the pharmacophore fingerprints is fast and a reasonably large number of molecules can be handled. The speed of these calculations permits the user to readily add to the overall procedure more information about the target or active compounds as probes in the ligand based virtual screening. 

Ligand-Based Virtual Screening (2-D Similarity Search, 3-D Pharmacophore Search)... 

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