Charge reversal mutations in mesophilic-thermophilic orthologous protein pairs and their role in enhancing coulombic interaction energy

Abstract

Proteins from thermophilic organisms are a matter of immense interest for decades because of its application in fields like de-novo protein design, thermostable variants of biocatalysts etc. Previous studies have found several sequence and structural adaptations related to thermal stability, while charge reversal study remains ignored. Here we address whether charge reversal mutations naturally occur in mesophilic-thermophilic/hyperthermophilic orthologous proteins. Do they contribute to thermal stability? Our systematic study on 1550 mesophilic-thermophilic/hyperthermophilic orthologous protein pairs with remarkable structural and topological similarity, shows gain in coulombic interaction energy in thermophilic/hyperthermophilic proteins at short range associated with partially exposed and buried charge reversal mutations, which may enhance thermostability. Our findings call forth its application in future protein engineering studies.

Communicated by Ramaswamy H. Sarma

Keywords:

• Protein thermostability
• thermal adaptation
• coulombic interaction
• charge reversal mutation
• solvent interaction

Acknowledgement

S.H. is supported by DBT-BINC SRF fellowship (Fellow Number: DBT-BINC/2017/CU/12).

The authors acknowledge Soumya Kundu and Raktim Maity for their valuable comments during the discussions. The authors would also like to acknowledge the anonymous referees for their valuable suggestions.

Disclosure statement

No potential conflict of interest was reported by the authors.

Author contribution

S.H. and S.K. designed research; S.H. implemented computational methodologies, S.H. and S.B. performed research; all analyzed data and wrote the paper.

Additional information

Funding

S.H. is supported by DBT-BINC SRF fellowship (Fellow Number: DBT-BINC/2017/CU/12).