Article

Molecular binding: Under water's influence

Gerhard Hummer is in the Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, USA. .
Nature Chemistry (Impact Factor: 25.33). 11/2010; 2(11):906-7. DOI: 10.1038/nchem.885
Source: PubMed
ABSTRACT
Hydration is known to affect molecular-recognition processes, such as those between proteins and ligands. Now, theoretical simulations provide thermodynamic insight into cavity-ligand binding, revealing how it is predominantly driven by the behaviour of the few surrounding water molecules.

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    • "The analysis of the structure and dynamic properties of the solvent around protein active sites, has gathered strong attention among the scientific community, showing that the water molecules that are displaced upon ligand binding are key players for determining the underlying thermodynamics of the process (Michel et al. 2009; Hummer 2010; Setny et al. 2010 ). As a result of the protein–solvent interactions , water molecules are not placed randomly on the protein surface, adopting thus a well-established structure, defined by regions of highly ordered water molecules. "
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    • "Recent simulations on a model system addressed this question. Through the use of umbrella sampling calculations at multiple temperatures on the simple model system of a spherical ligand binding into a hemispherical cavity, Baron et al. decomposed the entropic and enthalpic contributions to ligand binding or rejection for neutral and charged ligands binding to neutral and charged receptors (Baron et al. 2010; Hummer, 2010; Setny et al. 2010). Results demonstrated that water dominated the binding thermodynamics. "
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