Enhanced conformational fluctuations during protein reactions

Abstract

Proteins are flexible systems and their structures fluctuate at room temperature in aqueous solution due to the thermal energy. Although the role of conformational fluctuations in protein reactions has been an attractive and challenging subject to elucidate reaction mechanisms, there has been no direct experimental detection of such fluctuations during reactions. In this review, several time-resolved measurements of thermody-namic properties, which are directly linked to the fluctuation of proteins, are presented. In all cases, the fluctuations determined from the thermal expansion volume and the compressibility are enhanced in short-lived intermediates, and are well correlated with the reactivities. These results show that fluctuation is indeed key to understanding why some proteins can react without significant conformational changes.