The first part of this paper contains an overview of protein structures, their
spontaneous formation ("folding"), and the thermodynamic and kinetic aspects of this
phenomenon, as revealed by in vitro and in vivo experiments. It is stressed that
universal features of the in vitro folding are observed near the point of thermodynamic
equilibrium between the native and denatured states of the protein. Here the "two-state"
("denatured state" ↔ "native state") transition proceeds without accumulation of
metastable intermediates; this facilitates investigation of the "transition state". This
state, which is the most unstable in the folding pathway, and its structured core (a
"nucleus") are distinguished by their essential influence on the folding/unfolding
kinetics. In the second part of the paper, a theory of protein folding rates and related
phenomena is presented. First, it is shown that the protein size determines the range of a
protein’s folding rates in the vicinity of the point of thermodynamic equilibrium
between the native and denatured states of the protein. Then, we present methods for
calculating folding and unfolding rates of globular proteins from their sizes, stabilities
and either 3D structures or amino acid sequences. Finally, we show that the same theory
outlines the location of the protein folding nucleus (i.e., the structured part of the
transition state) in reasonable agreement with experimental data.
Keywords: Native protein structure, denatured protein, spontaneous protein
folding, folding intermediates, transition state, folding nucleus, folding rate,
Levinthal paradox, unfolding rate, mid-transition.