Explicit Characterization of the Free Energy Landscape of pKID-KIX Coupled Folding and Binding.

ABSTRACT: The most fundamental aspect of the free energy landscape of proteins is that it is globally funneled such that protein folding is energetically biased. Then, what are the distinctive characteristics of the landscape of intrinsically disordered proteins, apparently lacking such energetic bias, that nevertheless fold upon binding? Here, we address this fundamental issue through the explicit characterization of the free energy landscape of the paradigmatic pKID-KIX system (pKID, phosphorylated kinase-inducible domain; KIX, kinase interacting domain). This is done based on unguided, fully atomistic, explicit-water molecular dynamics simulations with an aggregated simulation time of >30 μs and on the computation of the free energy that defines the landscape. We find that, while the landscape of

SUBMITTER: Chong SH 

PROVIDER: S-EPMC6716127 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature