Origin of heat capacity changes in a "nonclassical" hydrophobic interaction.
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ABSTRACT:
SUBMITTER: Syme NR
PROVIDER: S-EPMC2435424 | biostudies-literature | 2007 Sep
REPOSITORIES: biostudies-literature
Publications
Origin of heat capacity changes in a "nonclassical" hydrophobic interaction.
Syme Neil R NR Dennis Caitriona C Phillips Simon E V SE Homans Steve W SW
Chembiochem : a European journal of chemical biology 20070901 13
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Project description:The heat capacity change, ΔCp, accompanying the folding/unfolding of macromolecules reflects their changing state of hydration. Thermal denaturation of the DNA duplex is characterized by an increase in ΔCp but of much lower magnitude than observed for proteins. To understand this difference, the changes in solvent accessible surface area (ΔASA) have been determined for unfolding the B-form DNA duplex into disordered single strands. These showed that the polar component represents ~ 55% of the total increase in ASA, in contrast to globular proteins of similar molecular weight for which the polar component is only about 1/3rd of the total. As the exposure of polar surface results in a decrease of ΔCp, this explains the much reduced heat capacity increase observed for DNA and emphasizes the enhanced role of polar interactions in maintaining duplex structure. Appreciation of a non-zero ΔCp for DNA has important consequences for the calculation of duplex melting temperatures (Tm). A modified approach to Tm prediction is required and comparison is made of current methods with an alternative protocol.
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Project description:It has been suggested that heat capacity changes in enzyme catalysis may be the underlying reason for temperature optima that are not related to unfolding of the enzyme. If this were to be a common phenomenon, it would have major implications for our interpretation of enzyme kinetics. In most cases, the support for the possible existence of a nonzero (negative) activation heat capacity, however, only relies on fitting such a kinetic model to experimental data. It is therefore of fundamental interest to try to use computer simulations to address this issue. One way is simply to calculate the temperature dependence of the activation free energy and determine whether the relationship is linear or not. An alternative approach is to calculate the absolute heat capacities of the reactant and transition states from plain molecular dynamics simulations using either the temperature derivative or fluctuation formula for the enthalpy. Here, we examine these different approaches for a designer enzyme with a temperature optimum that is not caused by unfolding. Benchmark calculations for the heat capacity of liquid water are first carried out using different thermostats. It is shown that the derivative formula for the heat capacity is generally the most robust and insensitive to the thermostat used and its parameters. The enzyme calculations using this method give results in agreement with direct calculations of activation free energies and show no sign of a negative activation heat capacity. We also provide a simple scheme for the calculation of binding heat capacity changes, which is of clear interest in ligand design, and demonstrate it for substrate binding to the designer enzyme. Neither in that case do the simulations predict any negative heat capacity change.
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