Molecular simulations suggest protein salt bridges are uniquely suited to life at high temperatures.

A series of explicit solvent molecular dynamics simulations has been performed to investigate the temperature dependence of salt bridge interactions between two freely diffusing amino acids. The simulations, performed at 25, 50, 75, and 100 °C, allow a large number of distinct association and dissociation events to be directly observed, without the imposition of additional forces to drive association. Analysis of contact frequencies for atom pairs demonstrates that the number of salt bridge contacts between the two molecules is unaffected by temperature, whereas the numbers of hydrophobic and polar contacts are greatly diminished. A second, independent set of simulationsusing rigid, prototypical molecule typesallows the differing temperature dependences of hydrophobic, polar, and salt bridge interactions to be unambiguously examined. In the prototype molecule simulations, the salt bridge interaction is found to substantially increase in stability at 100 °C relative to 25 °C. This difference in behavior be...