(747b) Role of Secondary Structure in Protein Liquid-Liquid Phase Separation Highlighted By a New Coarse-Grained Model
We present an extension to our original CG model , which now incorporates pseudo angle and pseudo dihedral potentials parametrized using experimental data and allows us to quantitatively capture the helical propensity. We show that the alpha helical and the PPII fractions obtained using CG simulations follow both the trend and the magnitude of the experimental NMR results. Using TDP-43 as a model system, we demonstrate the ability of this model to faithfully capture the role of secondary structure in LLPS. Particularly, we focus on the existence of a cooperative alpha helical region between the residues 331-340 , and show that designed, or ALS-related mutations in this region alter the local helical content, and LLPS of the full sequence.
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