Factors Promoting the Formation of Clathrate-Like Ordering of Water in Biomolecular Structure at Ambient Temperature and Pressure.

Clathrate hydrate forms when a hydrophobic molecule is entrapped inside a water cage or cavity. Although biomolecular structures also have hydrophobic patches, clathrate-like water is found in only a limited number of biomolecules. Also, while clathrate hydrates form at low temperature and moderately higher pressure, clathrate-like water is observed in biomolecular structure at ambient temperature and pressure. These indicate presence of other factors along with hydrophobic environment behind the formation of clathrate-like water in biomolecules. In the current study, we presented a systematic approach to explore the factors behind the formation of clathrate-like water in biomolecules by means of molecular dynamics simulation of a model protein, maxi, which is a naturally occurring nanopore and has clathrate-like water inside the pore. Removal of either confinement or hydrophobic environment results in the disappearance of clathrate-like water ordering, indicating a coupled role of these two factors. Apart from these two factors, clathrate-like water ordering also requires anchoring groups that can stabilize the clathrate-like water through hydrogen bonding. Our results uncover crucial factors for the stabilization of clathrate-like ordering in biomolecular structure which can be used for the development of new biomolecular structure promoting clathrate formation.