THE MOLTEN GLOBULE IS A 3RD THERMODYNAMICAL STATE OF PROTEIN MOLECULES

Analysis of published data on conformational transitions in relatively small proteins shows that the slopes of these transitions are proport ional to the protein molecular weight. It is true both for transitions from the native (N) to the unfolded (U) states (when protein denatura tion is coupled to its unfolding) and for transitions from the native to the molten globule (MG) states and from the molten globule to the u nfolded state (when protein denaturation is decoupled from protein unf olding). This is precisely the behaviour predicted by thermodynamics f or first order phase transitions ('all-or-none' transitions) in small systems. It follows that N --> U, N --> MG and MG --> U transitions in proteins are all of the 'all-or-none' type. Thus the molten globule s tate of protein molecules is separated by an 'all-or-none' transition both from the native and the unfolded state, i.e. the molten globule s tate is a third thermodynamic state of protein molecules in addition t o the two previously established states - the native and the unfolded.