Relative importance of the intrinsic properties of the polypeptide chain vis-a-vis the environmental influences, in driving the folding of a protein, has been a subject of extensive debate and investigation. Folding/misfolding lead to self association in many systems, which have biological functional significance. We compare here, the NMR derived equilibrium folding transitions driven under different environmental conditions in the GTPase Effector Domain of dynamin, which self-associates into megadalton size species. We conclude that though hierarchy of folding and association of GED is substantially influenced by the solvents, these properties, to a good extent are also driven by intrinsic properties of the polypeptide chain, and the regions that form secondary structures, the types of secondary structures formed in those regions, and finally the regions that participate in the self-association are the same, indicating near neighbor interactions would have a telling effect on the final outcome of the folding process. These observations would open a new reliable frontier for elucidating the multiple folding trajectories and consequent self-association, by simulations in vacuum, for this protein.
Keywords: Association, denatured state, dimethyl sulfoxide, guanidine-hydrochloride, GTPase effector domain, folding landscape, nuclear magnetic resonance, polypeptide chain, biochemical signals, Chemical denaturation.