Computer Simulation Studies of Solvation Thermodynamics

Division Of Basic Sciences - Nci

Investigators

Abstract

In this period we published a paper that extended our previous work by examining the temperature-dependence of free energies and forces among small model hydrophilic and hydrophobic functional groups of proteins. For the hydrophilic solutes, different relative orientations were used to distinguish between direct, inter-solute hydrogen bonds, and solutes simultaneously hydrogen bonding to a solvent water bridge. Interestingly, the temperature dependencies of the hydrophobic and directly hydrogen bonding solutes turned out to be opposite to that of the bridged hydrophilic solutes: with the delta-G becoming more negative for the former and less negative for the latter with increasing temperature. Dissection of the free energy curves into enthalpy and entropy contributions, and further separation of the enthalpy term into solute-solute, solute-solvent and solvent-solvent components provided insight into the physical molecular causes for the distinctive thermodynamic results. Finally, it was reasoned how the opposite temperature dependencies of the two types of hydrophilic interactions provides a rational for the cold denaturation of proteins.