Approaches to efficiently estimate solvation and explicit water energetics in ligand binding

The use of WaterMap

Yue Yang, Felice C Lightstone, Sergio E. Wong

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)277-287
Number of pages11
JournalExpert Opinion on Drug Discovery
Volume8
Issue number3
DOIs
StatePublished - Mar 2013
Externally publishedYes

Fingerprint

Ligands
Streptavidin
Water
Water Purification
Expert Testimony
Drug Discovery
Biotin
Thermodynamics
Protein Binding
Costs and Cost Analysis
Lead

Keywords

  • Computation
  • Drug discovery
  • Solvent
  • WaterMap

ASJC Scopus subject areas

  • Drug Discovery

Cite this

Approaches to efficiently estimate solvation and explicit water energetics in ligand binding : The use of WaterMap. / Yang, Yue; Lightstone, Felice C; Wong, Sergio E.

In: Expert Opinion on Drug Discovery, Vol. 8, No. 3, 03.2013, p. 277-287.

Research output: Contribution to journalArticle

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