Electrostatic contributions to heat capacity changes of DNA-ligand binding.
Significant heat capacity changes (DeltaCp) 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 DeltaCp 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 DeltaCp 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 DeltaCp associated with binding for DNA binding reactions involving the ligands DAPI, netropsin, lexitropsin, and the lambda repressor binding domain.
The Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6059 USA.
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D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D006690:Bisbenzimidazole / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D006358:Hot Temperature; D007211:Indoles / Q000737:chemistry / Q000378:metabolism; D007364:Intercalating Agents / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008956:Models, Chemical; D009429:Netropsin / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism; D055672:Static Electricity; D013816:Thermodynamics; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D007211:Indoles; D007364:Intercalating Agents; D008024:Ligands; D012097:Repressor Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C016649:phage repressor proteins; C053654:lexitropsin; C007293:DAPI; D009429:Netropsin; D004247:DNA; D006690:Bisbenzimidazole