Stability of buried and networked salt-bridges (BNSB) in thermophilic proteins

Abstract

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.

Comparative physicochemical and evolutionary study of SARS-CoV-2 and SARS with special reference to salt bridge and their microenvironment: A plausible explanation for divergency, stability and severity of SARS-CoV-2

“…Four types of energy terms were calculated in this analysis; desolvation (ΔΔG dslv ), bridge (ΔΔG brd ), background (ΔΔG bac ), total net energy (ΔΔG net ). NUM method [38] was used to calculate network salt bridge energies. Those salt bridge residues surrounded by charged, polar and hydrophobic residues which might affect those salt bridge energies.…”

Intrinsic basis of thermostability of prolyl oligopeptidase from Pyrococcus furiosus

“…Salt-bridge is usually of two types, namely IP and NU. net ( ΔΔG net ) and component (desolvation: ΔΔG dslv , bridge: ΔΔG brd and background: ΔΔG bac ) energy terms of salt-bridge are extracted by applying IPM in the case of the former 36 – 39 and NUM in the case of the latter 40 . Desolvation of salt-bridge residues is a thermodynamically uphill process and thus, ΔΔG dslv is always positive.…”

“…On the other hand, the interaction energy ( ΔΔG brd ) of positive and negative charges is always negative. ΔΔG bac , on the other hand, which interacts with salt-bridge's partners and whose candidates are originating from the sequence, maybe favorable or unfavorable 40 , 41 . The amount of ΔΔG net was found to be highly favorable in the case of hyperthermophilic glutamate dehydrogenase than that of its mesophilic counterpart 36 , 42 .…”

“…Nevertheless, the intrinsic basis of protein thermostability 2 remains unknown today. Here, the knowledge of the microenvironment (ME) of protein seems to be central 40 . Notably, while ΔΔG dslv and ΔΔG brd provide partners of salt-bridge specific details, ΔΔG bac is related to other residues of protein 36 – 40 , 42 .…”

“…Here, the knowledge of the microenvironment (ME) of protein seems to be central 40 . Notably, while ΔΔG dslv and ΔΔG brd provide partners of salt-bridge specific details, ΔΔG bac is related to other residues of protein 36 – 40 , 42 . A ME of a salt-bridge is the residues that are interacting with the partners of salt-bridge beyond four Å distance (in the case of charged residues) under a given cut-off of the energy.…”