Jan 22, 2016

Folding PDZ2 domain using the Molecular Transfer Model

BioRxiv : the Preprint Server for Biology
Zhenxing LiuDave Thirumalai


A major challenge in molecular simulations is to describe denaturant-dependent folding of proteins order to make direct comparisons with in vitro experiments. We use the molecular transfer model (MTM), which is currently the only method that accomplishes this goal albeit phenomenologically, to quantitatively describe urea-dependent folding of PDZ domain, which plays a significant role in molecular recognition and signaling. Experiments show that urea-dependent unfolding rates of the PDZ2 domain exhibit a downward curvature at high urea concentrations ([ C ]s), which has been interpreted by invoking the presence of a sparsely populated high energy intermediate. Simulations using the MTM and a coarse-grained Self-Organized Polymer (SOP) representation of PDZ2 are used to show that the intermediate ( IEQ ), which has some native-like character, is present in equilibrium both in the presence and absence of urea. The free energy profiles as a function of the structural overlap order parameter show that there are two barriers separating the folded and unfolded states. Structures of the transition state ensembles, ( TSE 1 separating the unfolded and ( IEQ ) and TSE 2 separating IEQ and the native state), determined using the Pfold met...Continue Reading

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Mentioned in this Paper

Biochemical Pathway
Small Angle X Ray Scattering
Plain X-ray
Spatial Distribution
X-linked Centronuclear Myopathy
Urea Measurement

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