Kinetic coherence underlies the dynamics of disordered proteins.

ABSTRACT: The dynamics of two proteins of similar size, the globular lysozyme and the intrinsically disordered Huntingtin interacting protein, has been simulated in three states resembling a globule, a pre-molten globule, and a molten globule. A coherence time τ has been defined, measuring the delay in the display of a stochastic behaviour after a perturbation of the system. This time has been computed for two sets of collective variables: the projection of the phase point onto the positions and momenta subspaces (τ _r and τ _p ), and the principal components (PCs) of positions q and momenta π produced by a covariance analysis in these subspaces (τ _q and τ _π ). In all states τ _p ≈ 3.5τ _r , and τ _π ≈ 3.5τ _q . The coherence times of individual PCs, τ ^(l) _q and τ ^(l) _π, have also been computed, and τ ^(l) _π > τ ^(l) _q in all states. The prevalence of τ _p over τ _r , or of τ _π over τ _q , drives the dynamics of the protein over a time range of ≈1-2 ps; moreover, a hidden synchronism appears to raise the momenta subspace's coherence above that of its individual PCs. In the transition of lysozyme to the molten globule the τ ^(l) _q decrease but, unexpectedly, the τ ^(l) _π increase; after this transition τ _p ≈ 5τ _r and τ _π ≈ 5τ _q . A gain of kinetic coherence accompanies thus the loss of structural coherence caused by the denaturation of the protein in the transition from globule to molten globule. The increase of the τ ^(l) _π does not take place in the analogous transition of the Huntingtin protein. These results are compared with those of a similar analysis performed on three pseudo-proteins designed by scrambling the primary sequence of the Huntingtin interacting protein, and on two oligopeptides. The hidden synchronism appears to be a generic property of these polypeptides. The τ ^(l) _π spectrum is similar in denaturated and in intrinsically disordered biomolecules; but the gain of kinetic coherence as a result of denaturation seems to be a specific property of the biologically functional lysozyme.

SUBMITTER: Tenenbaum A 

PROVIDER: S-EPMC9043365 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature