Document Detail


Substantial improvements in large-scale redocking and screening using the novel HYDE scoring function.
MedLine Citation:
PMID:  22203423     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The HYDE scoring function consistently describes hydrogen bonding, the hydrophobic effect and desolvation. It relies on HYdration and DEsolvation terms which are calibrated using octanol/water partition coefficients of small molecules. We do not use affinity data for calibration, therefore HYDE is generally applicable to all protein targets. HYDE reflects the Gibbs free energy of binding while only considering the essential interactions of protein-ligand complexes. The greatest benefit of HYDE is that it yields a very intuitive atom-based score, which can be mapped onto the ligand and protein atoms. This allows the direct visualization of the score and consequently facilitates analysis of protein-ligand complexes during the lead optimization process. In this study, we validated our new scoring function by applying it in large-scale docking experiments. We could successfully predict the correct binding mode in 93% of complexes in redocking calculations on the Astex diverse set, while our performance in virtual screening experiments using the DUD dataset showed significant enrichment values with a mean AUC of 0.77 across all protein targets with little or no structural defects. As part of these studies, we also carried out a very detailed analysis of the data that revealed interesting pitfalls, which we highlight here and which should be addressed in future benchmark datasets.
Authors:
Nadine Schneider; Sally Hindle; Gudrun Lange; Robert Klein; Jürgen Albrecht; Hans Briem; Kristin Beyer; Holger Claußen; Marcus Gastreich; Christian Lemmen; Matthias Rarey
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-27
Journal Detail:
Title:  Journal of computer-aided molecular design     Volume:  -     ISSN:  1573-4951     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8710425     Medline TA:  J Comput Aided Mol Des     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Center for Bioinformatics, University of Hamburg, Bundesstr. 43, 20146, Hamburg, Germany.
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