Investigating differences between thermodynamically and kinetically stable subtilisins to identify sequence signatures of kinetic stability.

Abstract

A protein's energy landscape, including the thermodynamic stability and dynamics of all accessible conformations, is encoded in its primary sequence. While the field has come a long way in understanding how thermodynamics are encoded, how the sequence encodes kinetic barriers is still poorly understood. For decades, researchers have attempted to uncover the sequence signatures of kinetically stable proteins by studying proteins with extreme kinetic barriers, such as extracellular proteases. It has been postulated that secreted proteases evolved large barriers to minimize local fluctuations that would leave them susceptible to damage in the harsh extracellular environment, including degradation by other proteases.