The role of water in drug–receptor interactions

Abstract

The idea that liquid water is not a uniform and random arrangement of molecules has been taken very seriously by the scientific community. Many experimental and computational investigations show that clathrate- or ice-like structures probably exist at a short time scale in solution. We have designed a new program to simulate water structure around solutes. Our model is based on the geometrical constraints of hydrogen bonding in order to be capable of producing clathrate-like structures. Simulations with small molecules and bio-molecules, using the new software, produce networks of water with specific patterns made of small water rings. The water structures built are consistent with the classification of molecules in terms of structure breaking and making. This approach may give insight into, and a more accurate description of, drug–receptor interactions. The results also suggest that water structure may impart sufficient energy to modify the conformational space of organic molecules through hydrogen bonding.

Keywords::

• Water structure
• structure maker
• structure breaker
• drug–receptor interaction
• clathrate
• simulation

Acknowledgement

This work was made possible by funding from AstraZeneca (Loughborough, UK).