jz7b02021_si_001.pdf (1.55 MB)
A Universal Pattern in the Percolation and Dissipation of Protein Structural Perturbations
journal contribution
posted on 2017-09-14, 00:00 authored by Nandakumar Rajasekaran, Ashok Sekhar, Athi N. NaganathanUnderstanding the
extent to which information is transmitted through
the intramolecular interaction network of proteins upon a perturbation,
that is, an allosteric effect, has long remained an unsolved problem.
Through an analysis of high-resolution NMR data from the literature
on 28 different proteins and 49 structural perturbations, we show
that the extent of induced structural changes through mutations and
molecular events including protein–protein, protein–peptide,
protein–ligand binding, and post-translational modifications
exhibit a near-universal exponential functional form. The extent of
percolation into the protein structures can be up to 20–25
Å despite no apparent change in the 3D structures. These observations
are also consistent with theoretical expectations, elementary graph
theoretic analysis of protein structures, detailed molecular dynamics
simulations, and experimental double-mutant cycles. Our analysis highlights
that most molecular events would contribute to allosteric effects
independent of protein structure, topology, or identity and provides
a simple avenue to test and potentially model their effects.