Specificity versus stability in computational protein design.

ABSTRACT: Protein-protein interactions can be designed computationally by using positive strategies that maximize the stability of the desired structure and/or by negative strategies that seek to destabilize competing states. Here, we compare the efficacy of these methods in reengineering a protein homodimer into a heterodimer. The stability-design protein (positive design only) was experimentally more stable than the specificity-design heterodimer (positive and negative design). By contrast, only the specificity-design protein assembled as a homogenous heterodimer in solution, whereas the stability-design protein formed a mixture of homodimer and heterodimer species. The experimental stabilities of the engineered proteins correlated roughly with their calculated stabilities, and the crystal structu

SUBMITTER: Bolon DN 

PROVIDER: S-EPMC1200299 | biostudies-literature | 2005 Sep

REPOSITORIES: biostudies-literature