Molecular simulations of mutually exclusive folding in a two-domain protein switch.

ABSTRACT: A major challenge with testing designs of protein conformational switches is the need for experimental probes that can independently monitor their individual protein domains. One way to circumvent this issue is to use a molecular simulation approach in which each domain can be directly observed. Here we report what we believe to be the first molecular simulations of mutually exclusive folding in an engineered two-domain protein switch, providing a direct view of how folding of one protein drives unfolding of the other in a barnase-ubiquitin fusion protein. These simulations successfully capture the experimental effects of interdomain linker length and ligand binding on the extent of unfolding in the less stable domain. In addition, the effect of linker length on the potential for oligomeri

SUBMITTER: Mills BM 

PROVIDER: S-EPMC3030150 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature