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

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.