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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM054105-03
Application #
2701735
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Project Start
1996-05-01
Project End
2000-04-30
Budget Start
1998-05-01
Budget End
2000-04-30
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Biochemistry
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Prabhu, Ninad; Sharp, Kim (2006) Protein-solvent interactions. Chem Rev 106:1616-23