The slowly relaxing local structure perspective of protein dynamics by NMR relaxation

Abstract

NMR relaxation is a powerful method for elucidating structural dynamics. Standard stochastic dynamic models generate time correlation functions (TCFs) that feature physically well-defined parameters. We developed such a model, called the slowly relaxing local structure (SRLS) approach, for proteins. SRLS is a two-body (protein and probe) coupled-rotator approach. Given that the protein (featuring diffusion tensor, D1) restricts the probe (featuring diffusion tensor, D2), the two "bodies" are inherently coupled dynamically. This is substantiated by a local potential, u, associated with a local ordering tensor, S. SRLS allows for general tensorial properties of D1, D2, S and the magnetic NMR tensors, and a general form of u. The TCFs are multiexponential, in accordance with the degree of generality of the various tensors. The traditional model-free (MF) method is based on a different conceptualization. According to it a mode-decoupling bi-exponential (one term for each rotator) TCF captures adequately the detectable features of structural dynamics. Hence, stochastic approaches are unnecessary. Here, we show that this (amply proven) oversimplification leads to physically vague constructs/composites as descriptors of structural dynamics. We illustrate misleading results obtained with MF when mode coupling, or S tensor asymmetry, dominate the analysis. Finally, we delineate the substantial advantage in using SRLS TCF as quantity to be compared with its atomistic molecular dynamics-based counterpart. © 2014 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim.