A synthetic picture of intramolecular dynamics of proteins. Towards a contemporary statistical theory of biochemical processes.

An increasing body of experimental evidence indicates the slow character of internal dynamics of native proteins. The important consequence of this is that theories of chemical reactions, used hitherto, appear inadequate for description of most biochemical reactions. Construction of a contemporary, truly advanced statistical theory of biochemical processes will need simple but realistic models of microscopic dynamics of biomolecules. In this review, intended to be a contribution towards this direction, three topics are considered. First, an intentionally simplified picture of dynamics of native proteins which emerges from recent investigations is presented. Fast vibrational modes of motion, of periods varying from 10(-14) to 10(-11) s, are contrasted with purely stochastic conformational transitions. Significant evidence is adduced that the relaxation time spectrum of the latter spreads in the whole range from 10(-11) to 10(5) s or longer, and up to 10(-7) s it is practically quasi-continuous. Next, the essential ideas of the theory of reaction rates based on stochastic models of intramolecular dynamics are outlined. Special attention is paid to reactions involving molecules in the initial conformational substrates confirmed to the transition state, which is realized in actual experimental situations. And finally, the two best experimentally justified classes of models of conformational transition dynamics, symbolically referred to as "protein glass" and "protein machine", are described and applied to the interpretation of a few simple biochemical processes, perhaps the most important result reported is the demonstration of the possibility of predominance of the short initial condition-dependent stage of protein involved reactions over the main stage described by the standard kinetics. This initial stage, and not the latter, is expected to be responsible for the coupling of component reactions in the complete enzymatic cycles as well as more complex processes of biological free energy transduction.