Design of modified proteins using knowledge-based approaches

PoPMuSiC (http://babylone.ulb.ac.be/popmusic) is a program that has been developed to predict rapidly changes in protein thermodynamic stability upon single-site mutations. We describe in this paper the theoretical model that underlies the PoPMuSiC software, and present a few applications to various issues of biological interest. In particular, we investigate the possible use of PoPMuSiC for the prediction of changes in protein-protein binding affinity upon mutation. We also summarize previous studies where PoPMuSiC has been used to modulate the relative stability of different protein structural states, to help the identification of mutations that stabilize and solubilize the Tobacco Etch Virus protease (TEV) and to detect structural weaknesses in proteins that are subject to domain swapping.