Thermophilic proteins function at high temperature, unlike mesophilic proteins. Thermo-stability of these proteins is due to the unique buried and networked salt-bridge (BNSB). However, it is known that the desolvation cost of BNSB is too high compared to other favorable energy terms. Nonetheless, it is known that stability is provided generally by hydrophobic isosteres without the need for BNSB. We show in this analysis that the BNSB is the optimal evolutionary design of salt-bridge to offset desolvation cost efficiently. Hence, thermophilic proteins with a high level of BNSB provide thermo-stability.
Keywords: Thermophilic protein; buried; desolvation cost; networked salt-bridge; novel method; stability.