Intramolecular dynamics and conformational transitions in enzymes

At a later stage, the concepts of protein dynamics were supplemented by the principle of the dynamic adaptation of the enzyme conformational structure to the substrate configuration in consecutive reactions to the enzyme. Such an adaptation promotes both the first step of precise orientation and the subsequent chemical steps, without allowing cleavage of the contacts needed for the chemical mechanism (Likhtenshtein, 1976, 1988a). 

In the 1960 s and 1970 s, much indirect evidence was obtained in favour of protein intramolecular mobility, i.e. the entropy and energy specificity of enzyme catalysis (Likhtenshtein, 1966, 1976a, b, 1979, 1988 Lumry and Rajender, 1970 Lumry and Gregory, 1986). The first observations made concerned the transglobular conformational transition during substrate-protein interaction (Likhtenshtein, 1976), the reactivity of functional groups inside the protein globule, and proteolysis. 

From the late 1960 s to the early 1970 s, more direct approaches to the investigation of protein dynamics were intensively developed. Such investigations featured the application of physical methods, such as physical labeling, NMR, optical spectroscopy, fluorescence, differential scanning calorimetry, and X-ray and neutron scattering. The purposeful application of the approaches made it possible to obtain detailed information on the mobility of different parts of protein globules and to compare this mobility with both the functional characteristics and stability of proteins, and with results of the theoretical calculation of protein dynamics. 

In addition to the direct methods of studying molecular dynamics, several physical methods, indirect but nonetheless providing valuable complementary information, are applied to the solving of dynamical problems. Among them are such methods as X-ray diffraction (Frauenfelder, and McMahon 2001 Frauenfelder et al., 1991, 2001), thermal broadening of chromophore absorption (Di Pace et al., 1992), and heat capacity (Lumry and Gregory, 1986). 

The principle advantage of the physical labeling method is the possibility of receiving direct information about the structure, mobility and local micropolarity of certain parts of a molecular object of any molecular mass. Developments in synthetic chemistry, biochemistry and site-directed mutagenesis have provided researchers with a wide assortment of labels and probes, and have paved the way for the specific modification of protein function groups, including enzyme active sites. 

---