Research Highlight

Water remedy

Biplab Das

doi:10.1038/nindia.2008.287 Published online 29 September 2008

A particular water molecule could enhance the efficacy of an anti-HIV drug, new research suggests1. The anti-HIV drug inhibits the activity of protease, an enzyme that helps the virus propagate in the host. The results might find use in development of more efficient anti-HIV drugs.

Well-ordered water molecules link protease enzymes and the enzyme-inhibitor systems. These water molecules are thought to contribute to the potency of the inhibitor. To pin down the precise role of these water molecules, the researchers resorted to computer-based simulation studies and six HIV protease-inhibitor systems. They considered 5286 water molecules. The analysis showed that 301 water molecules can make three or more hydrogen bonds.

Structural water molecule enhances the hydrogen bond dynamics at the interface of the HIV-protease inhibitor complex. This increases the binding affinity of the inhibitor to the protease system. "The implication is that a better drug can be synthesized by proper modification at the water bound region," says lead researcher Cherumuttathu H. Suresh.

"One may also think about a chemical modification of the existing drug, which will completely replace inhibitor-water-protease indirect hydrogen bonds with inhibitor-protease direct hydrogen bonds," he says. The study method can be easily extendable to the study of binding of small molecules in large protein structures, he concludes.

The authors of this work are from: Computational Modeling and Simulation Section, National Institute for Interdisciplinary Science and Technology, Trivandrum, India & Graduate School of Information Science, Nagoya University, Chikusa-ku, Nagoya, Japan.


  1. Suresh, H. C. et al. Role of Structural Water Molecule in HIV Protease-Inhibitor Complexes: A QM/MM Study. J Comput. Chem. 29, 1840-1849 (2008) | Article |