Protein dynamics and function from solution state NMR spectroscopy

Abstract

Abstract. It is well-established that dynamics are central to protein function; their importance is implicitly acknowledged in the principles of the Monod, Wyman and Changeux model of binding cooperativity, which was originally proposed in 1965. Nowadays the concept of protein dynamics is formulated in terms of the energy landscape theory, which can be used to understand protein folding and conformational changes in proteins. Because protein dynamics are so important, a key to understanding protein function at the molecular level is to design experiments that allow their quantitative analysis. Nuclear magnetic resonance (NMR) spectroscopy is uniquely suited for this purpose because major advances in theory, hardware, and experimental methods have made it possible to characterize protein dynamics at an unprecedented level of detail. Unique features of NMR include the ability to quantify dynamics (i) under equilibrium conditions without external perturbations, (ii) using many probes simultaneously, and (iii) over large time intervals. Here we review NMR techniques for quantifying protein dynamics on fast (ps-ns), slow (μs-ms), and very slow (s-min) time scales. These techniques are discussed with reference to some major discoveries in protein science that have been made possible by NMR spectroscopy.

Urea-Dependent Adenylate Kinase Activation following Redistribution of Structural States

“…Protein function is dependent on an intricate interplay among protein structure, stability, and dynamics where stability refers to the difference in free energy between the structural microstates that are dynamically sampled (37). Protein folding dynamics can be perturbed by addition of chaotropic denaturants such as urea and guanidinium hydrochloride, which stabilize the states in a dynamic ensemble with the largest SAS areas (unfolded states in protein folding reactions).…”

An optimal distance cutoff for contact-based Protein Structure Networks using side-chain centers of mass

“…Proteins are complex and highly dynamic entities attaining a myriad of different conformations in solution 1–5 that are often related to the protein function. Indeed, they can resemble bound states to a biological partner 6–10 , active states of enzymes 11–14 , or conformations that are stabilized by a post-translational modification (PTM) 6, 11 , as well as altered by a disease-related mutation 15 .…”

Protein crystal lattices are dynamic assemblies: the role of conformational entropy in the protein condensed phase

“…The subjects for which three-dimensional structures have been determined with high resolution are typically small proteins (<20 kDa); however, in some cases protein structures as large as 50 kDa have been determined with reasonable accuracy (Serrano, Aubol et al, 2016;Serrano, Dutta et al, 2016). NMR spectroscopy is used to characterize protein dynamics over a variety of time ranges from picoseconds to hours (Lange et al, 2008;Kovermann et al, 2016). On the other hand, the latter is a limitation of NMR because of the difficulty in quantifying dynamic motions that occur over wide ranges.…”