THE PROTEIN-CLASS ANALOGY - SOME INSIGHTS FROM HOMOPEPTIDE COMPARISONS

The question of the ''glassiness'' of hydrated protein systems is exam ined by comparing reported observations on proteins with the character istic features, both long time and very short time aspects, of the liq uid-to-glass transition in liquid and polymer systems. In an attempt t o reconcile conflicting features, the calorimetric behavior of the muc h-studied hydrophilic proteins, myoglobin and cytochrome c, has been d etermined by differential scanning calorimetry and compared with that of a model system, the hydrated monopeptide poly-L-asparagine of compa rable molecular weight. The results are analyzed in terms of the three canonical features of relaxation in glass-forming systems: non-Arrhen ius character (fragility), nonexponentiality, and nonlinearity. The ho mopeptide has a nonfreezing water range comparable to the ice-saturate d proteins, both native and denatured. Studies of the scan rate depend ence of T-g for a range of water contents from 14 to 29 wt % imply tha t the hydrated homopeptide system behaves as a ''strong'' liquid at al l water contents. We show that this is consistent with the behavior of native proteins according to earlier studies. However, anneal and sca n studies, particularly on hydrated cytochrome c, confirm the existenc e of an extremely broad distribution of relaxation times in the protei ns. From these observations, and from comparison with data on related systems, we conclude that hydrated proteins indeed may be classed amon g glass-forming systems, but due to their special structural features and to the disposition of the bound water, they show great departures from thermorheological simplicity. This seems to be partly a consequen ce of a special strengthening, in fully hydrated proteins, of the seco ndary (beta) relaxations which are not calorically important in most g lass-forming systems. We suggest that this may have developed to take advantage of the fast side chain dynamics typical of polymer systems a nd thereby to reduce the ambient temperature response times of biologi cally important processes. In the solution systems of this study, this feature smears out the glass transition almost beyond recognition. An analogy between the weakly first-order strong-to-fragile liquid trans ition in low-temperature water and the denaturing transition in protei ns is briefly discussed.