Virtual Screening on Homology Models

In the lack of X-ray structures, homology models are typically used for virtual screening. Homology models are obtained by comparative modeling using structural 

Copyright 2011 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 978-3-527-32636-5 

Homology Models versus Crystal Structures Comparative Evaluation of Screening Performance 

The performance of homology models depends on multiple factors that were thoroughly analyzed comparing the results with those obtained using X-ray structures [10]. In most cases, the performance of virtual screening was measured calculating enrichment factors. Enrichment factors (EEs) assess the quality of the rankings  

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Table 14.1 Successful structure-based virtual screening studies on homology models. 

Virtual Screening on the Homology Model of Histamine H4 Receptor [16]... 

Evers A, Klebe G. Successful virtual screening for a submicromolar antagonist of the neurokinin-1 receptor based on a ligand-supported homology model. J Med Ghent 2004 47 5381-92. 

Thus, EcR LBD homology models based on vertebrate nuclear receptor crystal structures, although instructive for general architecture and residue replacement, are, owing to their low sequence identity, rather speculative when used for ligand docking or as tools for virtual screens [164],... 

We performed a combined 2D and 3D analysis of chemical and biological space to identify ion channel privileged chemotypes. The 2D approach was based on a collection of biologically active compounds and consisted mainly of similarity and substructure searching and of analysis of common frameworks and fragments. Our 3D approach relied on multiple ion channel pharmacophores and homology models, which were used for virtual screening. 

For many protein drug targets crystal or solution structures are not available. In such cases homology models (130,131)and pseudoreceptor models (132) are often used. However, unless there is a very high conservation of receptor site residues the use of homology models for virtual screening is much riskier than using solved structures. On the other hand, the PDB contains a wealth of protein... 

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