Possible mechanism for the dynamic stabilization of protein structure

Abstract

There is an apparent contradiction between the long lifetime of the metastable structure of native proteins and the high rate of structural fluctuations, which result from the small activation energy required to change the native conformation. In this paper we point out that the observed stability of proteins is not a consequence of large potential barriers, but a result of the continuous reconstitution of the degraded structure by chain propagation. Polypeptide chains of proteins having naturally selected amino-acid sequences have regenerative ability which ensures the long lifetime of the native structure by making most of the fluctuations reversible. A simple calculation shows that in a certain fluctuation of an average protein molecule the probability of denaturation is less than 10 −25, therefore even the most rapid, picosecond time scale fluctuations cause spontaneous denaturation only in million year time scale. Hence, the generally observed spontaneous denaturation in vitro is rather a consequence of covalent structure modification or intermolecular interactions than a result of an intramolecular interconversion from the native conformation to another conformation.