Heat capacity, configurational entropy, and the role of ionic interactions in protein thermostability

Molecular dynamics simulation of solvated proteins at different temperatures can provide valuable descriptions of their global dynamics and their local fluctuations that can deepen our understanding of the molecular basis of protein thermostability. In this work a comparison of the dynamical behavior of homologous glutamate dehydrogenase domains from the hyperthermophilic bacterium Thermotoga maritima and the mesophilic bacterium Clostridium symbiosum as well as a molecular dynamics simulation study of a short polypeptide designed to fold into a trimeric coiled coil are reviewed with particular emphasis on the contribution of ion pairs and ionic networks to the conformational stability of the proteins. By considering the solvated proteins in their dynamic context thermodynamic properties such as electrostatic free energy differences, heat capacity and configurational entropy were calculated and suggested a new way of understanding protein thermostability on the basis of energetic fluctuations and accessible states. It appeared that a larger number of accessible degrees of freedom seems to accommodate the disorder caused by increased thermal motion.