Electrostatic Contributions to Heat Capacity Changes of DNA-Ligand Binding

Abstract

Significant heat capacity changes ( ΔC p) often accompany protein unfolding, protein binding, and specific DNA-ligand binding reactions. Such changes are widely used to analyze contributions arising from hydrophobic and polar hydration. Current models relate the magnitude of ΔC p to the solvent accessible surface area (ASA) of the molecule. However, for many binding systems—particularly those involving non-peptide ligands—these models predict a ΔC p that is significantly different from the experimentally measured value. Electrostatic interactions provide a potential source of heat capacity changes and do not scale with ASA. Using finite-difference Poisson-Boltzmann methods (FDPB), we have determined the contribution of electrostatics to the ΔC p associated with binding for DNA binding reactions involving the ligands DAPI, netropsin, lexitropsin, and the λ repressor binding domain.