Physical bases of thermal stability of proteins: A comparative study on homologous pairs from mesophilic and thermophilic organisms

We used classical molecular dynamics simulation method to investigate physical factors responsible for the increased thermal stability of proteins from thermophilic and hyperthermophilic organisms. Subject of investigation were two pairs of homologous proteins from the functional classes of: 1) cold shock proteins from Escherichia coli (mesophilic) and Bacillus caldolyticus (thermophilic) and 2) acylphosphatases from Bos taurus (mesophilic) and Pyrococcus horicoshii (hyperthermophilic). The simulations were performed for three different temperatures: 298 K, 373 K and 500 K. The results confirmed the common opinion that salt bridges and internal hydrogen bond networks stabilize thermostable proteins at high temperature. In addition, we found that at high temperatures the packing defects, in terms of cavity formation, increase with a preference to the mesophilic protein. Since cavities are a destabilizing factor, we conclude that due to specific packing organisation of proteins of extremophilic organisms, these proteins are more resistant to temperature induced cavity formation, which contributes to their enhanced tolerance towards increase in temperature.