Origin of Correlations between Local Conformational States of Consecutive Amino Acid Residues and Their Role in Shaping Protein Structures and in Allostery

By analyzing the Kubo-cluster-cumulant expansion of the
potential
of mean force of polypeptide chains corresponding to backbone-local
interactions averaged over the rotation of the peptide groups about
the Cα···Cα virtual
bonds, we identified two important kinds of “along-chain”
correlations that pertain to extended chain segments bordered by turns
(usually the β-strands) and to the folded spring-like segments
(usually α-helices), respectively, and are expressed as multitorsional
potentials. These terms affect the positioning of structural elements
with respect to each other and, consequently, contribute to determining
their packing. Additionally, for extended chain segments, the correlation
terms contribute to propagating the conformational change at one end
to the other end, which is characteristic of allosteric interactions.
We confirmed both findings by statistical analysis of the virtual-bond
geometry of 77 950 proteins. Augmenting coarse-grained and,
possibly, all-atom force fields with these correlation terms could
improve their capacity to model protein structure and dynamics.