Molecular dynamics study on protein and it's water structure at high pressure

We have performed NPT molecular dynamics simulations (Langevin Piston Metho d) on two types of solvated proteins-"denaturation-unfavorable" protein (in sulin) and "denaturation-favorable protein" (ribonuclease A) at high pressu re (from 1 bar up to 20 kbar). The method is based on the extended system f ormalism introduced by Andersen, where the deterministic equations of motio n for the piston degree of freedom are replaced by Langevin equation. We re port the structural changes of proteins (ribonuclease A and insulin) and wa ter molecules through radius of gyration, solvent accessible surface area, hydrogen bond pattern, and the topology of water clusters connected by the hydrogen bonded circular network. The solvent accessibility of ribonuclease A is mainly decreased by hydrophilic residues rather than hydrophobic resi dues under high pressure. From the results of hydrogen bond analysis, we ha ve found that alpha-helix is more stable than beta-sheet under high pressur e. In addition, from the analysis of the water cluster, we have observed th at for ribonuclease A, 5-membered ring structure is more favorable than 6-m embered ring at higher pressure. However, for insulin, the ratio of 5 to 6- ring is constant over the pressure ranges for which we have performed MD si mulation. This indicates that the water structure around insulin does not c hange under high pressure.