| Abstract
| - The temperature dependence of the interactions that stabilize protein structures is a long-standing issue, theelucidation of which would enable the prediction and the rational modification of the thermostability of atarget protein. It is tackled here by deriving distance-dependent amino acid pair potentials from four datasetsof proteins with increasing melting temperatures (Tm). The temperature dependence of the interactions isdetermined from the differences in the shape of the potentials derived from the four datasets. Note that,here, we use an unusual dataset definition, which is based on the Tm values, rather than on the livingtemperature of the host organisms. Our results show that the stabilizing weight of hydrophobic interactions(between Ile, Leu, and Val) remains constant as the temperature increases, compared to the other interactions.In contrast, the two minima of the Arg−Glu and Arg−Asp salt bridge potentials show a significant Tmdependence. These two minima correspond to two geometries: the fork−fork geometry, where the sidechains point toward each other, and the fork−stick geometry, which involves the Nε side chain atom ofArg. These two types of salt bridges were determined to be significantly more stabilizing at high temperature.Moreover, a preference for more-compact salt bridges is noticeable in heat-resistant proteins, especially forthe fork−fork geometry. The Tm-dependent potentials that have been defined here should be useful forpredicting thermal stability changes upon mutation.
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