Efforts to understand protein function at the molecular level have yet to fully capture the general rules that govern protein design. One important aspect of protein design is the prediction and optimization of enzyme stability over long time periods and under various harsh industrial operating conditions. This work presents a general method to directly improve the kinetic stability of an enzyme without reducing activity via a protein modeling-based approach. Enzyme function is conferred by intramolecular contacts between secondary structural units. By maintaining such interactions (and therefore the majority of residue-residue contacts) and intelligently changing the way in which those structural units are connected (i.e., changing the topology of the protein), we demonstrate that it is possible to change the rate of unfolding of a model protein, GFP, in vitro, directly effecting protein stability without effecting protein activity. This method may be universal and therefore applied to any protein with multiple structural units.