(76d) Disentangling the Stability and Function of Natively Unfolded Proteins

Natively unfolded proteins are emerging as an important class of biomacromolecules that carry out necessary biological functions despite their lack of well-defined three-dimensional structures, contrary to traditional ideas linking protein shape and function. In this talk, we present a series of computer simulation studies aimed at probing the stability and function of these disordered proteins. Using a coarse-grain model for unstructured polypeptides, we explore the effects of sequence composition (characterized by sequence hydrophobic and charge) and complexity (characterized by sequence non-randomness) on global conformational stability as a coil-globule transition. In addition to being able to probe the physics underlying the experimental charge/hydropathy and complexity correlations, our model provides insights into the joint correlation between orthogonal predictors for disordered sequences. In the final portion of this talk, we discuss ongoing simulations to explore the effects of sequence on the stability of helical peptides, as well as the water-mediated interactions between disordered phenylalaine-glycine repeat sequences that moderate gating of the nuclear pore complex.