Document Detail

Approaches to efficiently estimate solvation and explicit water energetics in ligand binding: the use of WaterMap.
MedLine Citation:
PMID:  23286874     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: Water displacement plays critical role in several phases of drug discovery. Proper treatment of displacing water could improve enrichment in virtual screening and could lead to more successes in lead optimization. WaterMap has recently emerged as a promising approach in this regard; recent implementations of this protocol successfully explained various binding activity that were poorly understood previously, including the well-known super affinity associated with biotin binding to streptavidin.
AREAS COVERED: The review briefly discusses implicit and explicit solvent models and focuses on an application of inhomogeneous solvation theory - WaterMap. Furthermore, the review discusses various successful cases where the use of WaterMap explained selectivity in protein-ligand binding and provides discussion of the fundamentals and recently successful implementations of WaterMap. The authors also discuss the limitations of this protocol and list a few approaches that could extend its implementation to more cases.
EXPERT OPINION: WaterMap is a powerful tool for calculating the cost of desolvation for structural waters. In some cases, it proved useful in predicting relative binding free energy differences for congeneric ligands. The practical utility of WaterMap hinges in adequate application of the results in the context of all the thermodynamic contributions to binding. Potential improvements as well as integration into methods such like MM-GB/SA could extend its success.
Yue Yang; Felice C Lightstone; Sergio E Wong
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Publication Detail:
Type:  Journal Article; Review     Date:  2013-01-04
Journal Detail:
Title:  Expert opinion on drug discovery     Volume:  8     ISSN:  1746-045X     ISO Abbreviation:  Expert Opin Drug Discov     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-22     Completed Date:  2013-08-06     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  101295755     Medline TA:  Expert Opin Drug Discov     Country:  England    
Other Details:
Languages:  eng     Pagination:  277-87     Citation Subset:  IM    
Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.
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MeSH Terms
Models, Molecular*
Protein Binding
Solvents / metabolism
Water / metabolism*
Reg. No./Substance:
0/Ligands; 0/Solvents; 7732-18-5/Water

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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