Modulation of folding energy landscape by charge-charge interactions: linking experiments with computational modeling.

ABSTRACT: The kinetics of folding-unfolding of a structurally diverse set of four proteins optimized for thermodynamic stability by rational redesign of surface charge-charge interactions is characterized experimentally. The folding rates are faster for designed variants compared with their wild-type proteins, whereas the unfolding rates are largely unaffected. A simple structure-based computational model, which incorporates the Debye-Hückel formalism for the electrostatics, was used and found to qualitatively recapitulate the experimental results. Analysis of the energy landscapes of the designed versus wild-type proteins indicates the differences in refolding rates may be correlated with the degree of frustration of their respective energy landscapes. Our simulations indicate that naturally occurr

SUBMITTER: Tzul FO 

PROVIDER: S-EPMC4311858 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature