Intrinsic disorder-based design of stable globular proteins

Abstract

Directed stabilization of globular proteins via substitution of a minimal number of amino acid residues is one of the most complicated experimental tasks. In this work, we have successfully used algorithms for the evaluation of intrinsic disorder predisposition (such as PONDR® FIT and IsUnstruct) as tools for searching for the weakened regions in structured globular proteins. We have shown that the weakened regions found by these programs as regions with highest levels of predicted intrinsic disorder predisposition are a suitable target for introduction of stabilizing mutations.

Keywords: Design of disulfide bond; Design of protein circular permutant; Intrinsically disorder propensity; Protein stability; Stable mutant proteins.