ProteoPlex: stability optimization of macromolecular complexes by sparse-matrix screening of chemical space.

Molecular machines or macromolecular complexes are supramolecular assemblies of biomolecules that ensure cellular homeostasis. Structure determination of those complexes in a purified state is often a tedious undertaking due to the compositional complexity and the related relative structural instability. To improve the stability of macromolecular complexes in vitro, we present here a generic method that optimizes the stability, homogeneity and solubility of macromolecular complexes by sparse-matrix screening of their thermal unfolding behaviour in the presence of various buffers and small molecules. The method includes the automated analysis of thermal unfolding curves based on a newly deve…