Dr. Sharp plans to simulate heat capacity changes, well-known to be important for protein folding and ligand binding, yet difficult to study by direct molecular dynamics simulation. He will develop a method to calculate hydration heat capacities, using a combination of the random network and explicit water models. Continuing preliminary work, the method will first be applied to small solutes, to understand at a molecular level why polar and non-polar groups have opposite specific heats of hydration. Proceeding with compounds that contain both polar and non-polar groups, the investigator will study the additivity of heat capacities. A rapid general calculation of hydration heat capacities will be developed that is more accurate than simple area methods; it will be tested on proteins whose heat capacities of unfolding have been accurately determined. Methods to evaluate chain configurational contributions will also be developed to deal with situations such as protein-ligand binding, where large heat capacity changes come from partial protein folding.
| Prabhu, Ninad; Sharp, Kim (2006) Protein-solvent interactions. Chem Rev 106:1616-23 |
