Multi-Timescale Dynamics in Intrinsically Disordered Proteins from NMR Relaxation and Molecular Simulation.
Related Articles Multi-Timescale Dynamics in Intrinsically Disordered Proteins from NMR Relaxation and Molecular Simulation.
J Phys Chem Lett. 2016 Jun 14;
Authors: Salvi N, Abyzov A, Blackledge M
Abstract
Intrinsically disordered proteins (IDPs) access highly diverse ensembles of conformations in their functional states. Although this plasticity is essential to their function, little is known about the dynamics underlying interconversion between accessible states. Nuclear Magnetic Resonance (NMR) relaxation rates contain a wealth of information about motion in IDPs, but the dynamic nature of IDPs complicates their interpretation. We present a novel framework in which Molecular Dynamics (MD) simulations are used in combination with experimental 15N relaxation measurements to characterize the ensemble of dynamic processes contributing to the observed rates. By accounting for the dynamic averaging present in the different conformational states sampled by the equilibrium ensemble, we are able to accurately describe both dynamic timescales and conformational sampling. The method is robust, systematically improving agreement with independent experimental relaxation data, irrespective of the actively targeted rates, and suggesting interdependence of motions occurring on timescales varying over three orders of magnitude.
PMID: 27300592 [PubMed - as supplied by publisher]
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