The many (polymeric) faces of intrinsically disordered proteins: Is a single Flory exponent enough?

Abstract

Proteins are biopolymers, composed of repeating sequence of amino acids (AA). In a typical sequence, the constituting AAs have different charges, hydrophobicity, and capacities to form directional and non-directional interactions. Such heterogeneity can results in sequences lacking a stable three dimensional structure. This class of proteins are intrinsically disordered protein (IDPs). A deeper understanding of IDPs require appropriate characterization of the conformations. To this end, scattering and single molecular spectroscopic measurements often assign a single Flory exponent (equivalently fractal dimension) to the IDPs. In this talk, I highlight limitation of this method by enhanced sampling of atomistic resolution conformations of disordered \beta-casein. I will show that the underlying energy landscape of the IDP contains a global minimum along with two shallow funnels. Employing static polymeric scaling laws separately for individual funnels, we find that they cannot be described by the same polymeric scaling exponent. Around the global minimum, the conformations are globular, whereas in the vicinity of local minima, we recover coil-like scaling. To elucidate the implications of structural diversity on equilibrium dynamics, we initiated standard MD simulations in the NVT ensemble with representative conformations from each funnel. Global and internal motions for different classes of trajectories show heterogeneous dynamics with globule to coil-like signatures. Thus, IDPs can behave as entirely different polymers in different regions of the conformational space.