All-atom contact potential approach to protein thermostability analysis

In this paper we use all-atom potential energy to define and analyze the inter-residue contacts in mesophilic and thermophilic proteins. Fifteen families of proteins are selected and each family has two representative proteins with greatly different preferred environmental temperatures. We find that both the number and energy of the contacts defined in this way show stronger correlations with the preferred temperatures of proteins than other factors used before. We also find that the charged-polar and charged-nonpolar residue contacts not only have larger contact numbers but also have lower single contact energies. Furthermore, the most important is that most of the thermophilic proteins have more charged-polar and charged-nonpolar residue contacts than their mesophilic counterparts. This suggests that they may play an important role in the thermostability of proteins, except usual charged-charged and nonpolar-nonpolar residue contacts. Charged residues may exert their profound influence by forming contacts not only with other charged residues but also with polar or nonpolar residues, thus further increasing the strength of contact network and then the thermostability of proteins.