A new heteropolymer theory to describe conformation of Intrinsically Disordered Proteins

Intrinsically Disordered Proteins (IDPs) perform many vital functions and yet have no native structure. This is in contrary to the commonly held notion that protein sequence determines the unique folded structure that in turn dictates the function of the protein. IDPs exhibit an ensemble of conformation, instead of a unique folded structure, making them amenable to tools of polymer statistical physics. Presently, homopolymer theories are commonly used in order to describe the conformation of IDPs. However, IDPs consist of amino acids of different chemical properties, including positive and negative charges. We present a novel heteropolymer theory to describe the sequence specific conformational ensemble of IDPs. Our theory provides rich ensemble average distance maps that are more informative about conformation than coarse-grain measures like radius of gyration or scaling exponents. We will showcase application of this novel analytical theory – benchmarked against all-atom simulations – to multiple naturally occurring IDPs. We highlight how biology can achieve variability with the ability to induce drastic conformational changes by making concise changes in the sequence – termed as hot spots -- such as post-translational modifications (PTMs), often used as a regulator.