Map Conformational Landscapes of Intrinsically Disordered Proteins with Polymer Physics Quantities

Biophys J. 2024 Apr 12:S0006-3495(24)00272-8. doi: 10.1016/j.bpj.2024.04.010. Online ahead of print.ABSTRACTDisordered proteins are conformationally flexible proteins that are biologically important and have been implicated in devastating diseases such as Alzheimer's and cancer. Unlike stably-folded structured proteins, disordered proteins sample a range of different conformations that needs to be accounted for. Here, we treat disordered proteins as polymer chains, and compute a dimensionless quantity called instantaneous shape ratio (Rs), as Rs = Ree2/Rg2, where Ree is end-to-end distance and Rg is radius of gyration. Extended protein conformations tend to have high Ree compared to Rg, and thus have high Rs values, whereas compact conformations have smaller Rs values. We use a scatter plot of Rs (representing shape) against Rg (representing size) as a simple map of conformational landscapes. We first examine the conformational landscape of simple polymer models such as Random Walk (RW), Self-Avoiding Walk (SAW) and Gaussian Walk (GW), and we notice that all protein/polymer maps lie within the boundaries of the GW map. We thus use the GW map as a reference and, to assess conformational diversity, we compute the fraction of the GW conformations (fC) covered by each protein/polymer. Disordered proteins all have high fC scores, consistent with their disordered nature. Each disordered protein accesses a different region of the reference map, revealing differences in their conform...
Source: Biophysical Journal - Category: Physics Authors: Source Type: research