Dynamic approaches to structural ensembles of intrinsically disordered proteins

Intrinsically disordered proteins a nd c omplex multidomain proteins are characterized by dynamic ensembles of conformations that cannot be unequivocally de scribed by t raditional s tatic te rms o f s tructural b iology. These states of proteins are critical in understanding their function at the atomic level, which will eventually lead to extending the structure-function paradigm to establish “unstructural biology” as a new field [1]. The functional importance of structural dynamics a nd complexity n ecessitates n ew s tandards an d pr otocols for the description of structural ensembles, also termed “supertertiary” structure in the case of very large proteins composed of a combination of folded and disordered elements [2]. Here we will 1) outline the development of a new database (pE-DB) that is designed to hold structural ensembles of proteins [3], 2) show through a few examples (PSD95, CBP) current experimental efforts to describe structural complexity at the supertertiary structural level, and 3) describe a novel bioinformatics tool, DynaMine, developed for predicting backbone dynamics from amino acid sequence.