Thermostabilization of industrially relevant proteins through computational design of medium range electrostatic interactions

Natural enzymes perform complex chemical transformations that can be used in industrial applications. However, these enzymes are adapted to their function within a living cell, not to the harsh environments that are often used in industrial processes. Thermophilic microorganisms have adapted to live at extreme temperatures and can provide insight into engineering enzymes for thermostability.
The adaptive nature by which thermophilic organisms survive harsh temperatures is correlated to their different protein structures. Attempts to classify the characteristics of thermophilic proteins have led to a better understanding of protein folding. In general, tighter Van der Waals interactions in the core of the protein, complex hydrogen bond networks, and the oligomeric state of proteins contribute to an increase in thermostability. The majority of studies on stabilizing factors of proteins have been done on how well the protein is packed and hydrogen bond networks with little attention given to medium range electrostatic interactions. Our objective is to design thermostable enzymes by introducing specific electrostatic terms into Rosetta via a knowledge based approach.


Alumni Project Members: Steven Combs, Brent Dorr