Protein Dynamics by NMR Spin Relaxation: The Slowly Relaxing Local Structure Perspective

Meirovitch, Eva; Polimeno, Antonino; Freed, Jack H.

doi:10.1002/9780470034590.emrstm1243

Cited by 10 publications

(67 citation statements)

References 71 publications

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“…The orientation of the OF frame with respect to the known dipolar tensor frame, DF, is given by the Euler angles Ω OF–DF = (α D , β D , 0). In previous SRLS studies of 15 N spin relaxation in proteins, 26–28 we found with data-fitting that β D = −101.3°. This corresponds to the main axis of the local ordering tensor, Z OF , pointing along

C_{i - 1}^{α} - C_{i}^{α}

.…”

Section: Resultsmentioning

confidence: 68%

“…22–24 The rotators are coupled by a local potential of mean torque, U , which represents the spatial restrictions exerted by the immediate protein surroundings at the site of the motion of the NMR probe. 25–28 The local order parameters (i.e., the principal values of the local ordering tensor, S ) are defined in terms of the potential U (see eqs 4 and 5 below). In the limit where the rotators are time scale separated (decoupled), the tensors D 1 and D 2 are isotropic, and the spatial restrictions are either very strong or very weak, axially symmetric, and centered at the Z-axis of all the magnetic tensors taken axial and collinear, one has D 2 = 1/(6τ e ) and

{false(S_{0}^{2} false)}^{2} = S^{2}

(where

S_{0}^{2}

is the axial order parameter).…”

Section: Theoretical Backgroundmentioning

confidence: 99%

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Analysis of ¹⁵N–¹H NMR Relaxation in Proteins by a Combined Experimental and Molecular Dynamics Simulation Approach: Picosecond–Nanosecond Dynamics of the Rho GTPase Binding Domain of Plexin-B1 in the Dimeric State Indicates Allosteric Pathways

et al. 2012

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We investigate ps-ns dynamics of the Rho-GTPase Binding Domain (RBD) of plexin-B1, which plays a key role in plexin-mediated cell signaling. Backbone 15N relaxation data of the dimeric RBD are analyzed with the model-free (MF) method, and with the slowly relaxing local structure/molecular dynamics (SRLS-MD) approach. Independent analysis of the MD trajectories, based on the MF paradigm, is also carried out. MF is a widely popular and simple method, SRLS is a general approach, and SRLS-MD is an integrated approach we developed recently. Corresponding parameters from the RBD dimer, a previously studied RBD monomer mutant, and the previously studied complex of the latter with the GTPase Rac1, are compared. The L2, L3 and L4 loops of the plexin-B1 RBD are involved in interactions with other plexin domains, GTPase binding, and RBD dimerization, respectively. Peptide groups in the loops of both the monomeric and dimeric RBD are found to experience weak and moderately asymmetric local ordering centered approximately at the Ci-1α-Ciα axes, and ns backbone motion. Peptide groups in the α-helices and the β-strands of the dimer (the β-strands of the monomer) experience strong and highly asymmetric local ordering centered approximately at the Ci-1α-Ciα axes (N–H bonds). N–H fluctuations occur on the ps time-scale. An allosteric pathway for GTPase binding, providing new insights into plexin function, is delineated.

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C_{i - 1}^{α} - C_{i}^{α}

.…”

Section: Resultsmentioning

confidence: 68%

{false(S_{0}^{2} false)}^{2} = S^{2}

(where

S_{0}^{2}

is the axial order parameter).…”

Section: Theoretical Backgroundmentioning

confidence: 99%

Analysis of ¹⁵N–¹H NMR Relaxation in Proteins by a Combined Experimental and Molecular Dynamics Simulation Approach: Picosecond–Nanosecond Dynamics of the Rho GTPase Binding Domain of Plexin-B1 in the Dimeric State Indicates Allosteric Pathways

et al. 2012

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“…We found previously that one has to account for structural asymmetry in order to obtain physically relevant result. 14–16 This can be accomplished in a straightforward manner by allowing for rhombic potentials. 14–16 However, the respective data-fitting calculations are demanding.…”

Section: Resultsmentioning

confidence: 99%

“…14–16 This can be accomplished in a straightforward manner by allowing for rhombic potentials. 14–16 However, the respective data-fitting calculations are demanding. The computation will become substantially more effective if structural asymmetry is accounted for within the scope of axial potentials by allowing for separate local ordering and local diffusion frames.…”

Section: Resultsmentioning

confidence: 99%

“…N–H sites in proteins residing in well-structured regions of the polypeptide were found to be associated with strong local potentials. 14–16 On the other hand, side-chain methyl sites in proteins were found to be associated with weak local potentials. 14–16 Although the strength of the local potentials in our examples might not be typical of many protein N–H and methyl sites, the diversity in symmetry is likely to be general in nature.…”

Section: Resultsmentioning

confidence: 99%

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Local Ordering at Mobile Sites in Proteins from Nuclear Magnetic Resonance Relaxation: The Role of Site Symmetry

2016

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Restricted motions in proteins (e.g., N–H bonds dynamics) are studied effectively with NMR. By analogy with restricted motions in liquid crystals (LC), the local ordering has in the past been primarily represented by potentials comprising the L = 2, |K| = 0, 2 spherical harmonics. However, probes dissolved in LC’s experience non-polar ordering, often referred to as alignment, while protein-anchored probes experience polar ordering, often referred to as orientation. In this study we investigate the role of local (site) symmetry in the context of the polarity of the local ordering. We find that potentials comprising the L = 1, |K| = 0, 1 spherical harmonics represent adequately polar ordering. It is useful to characterize potential symmetry in terms of the irreducible representations of D2h point group, which is already implicit in the definition of the rotational diffusion tensor. Thus, the relevant rhombic L = 1 potentials have B1u and B3u symmetry whereas the relevant rhombic L = 2 potentials have Ag symmetry. A comprehensive scheme where local potentials and corresponding probability density functions (PDFs) are represented in Cartesian and spherical coordinates clarifies how they are affected by polar and non-polar ordering. The Cartesian coordinates are chosen so that the principal axis of polar axial PDF is pointing along the z-axis, whereas the principal axis of the non-polar axial PDF is pointing along ±z. Two-term axial potentials with 1 ≤ L ≤ 3 exhibit substantial diversity; they are expected to be useful in NMR-relaxation-data-fitting. It is shown how potential coefficients are reflected in the experimental order parameters. The comprehensive scheme representing local potentials and PDFs is exemplified for the L = 2 case using experimental data from 15N-labeled plexin-B1 and thioredoxin, 2H-, and 13C-labeled benzenehexa-n-alkanoates, and nitroxide-labeled T4 lysozyme. Future prospects for improved ordering analysis based on combined atomistic and mesoscopic approaches are delineated.

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Multiscale modeling for interpreting nuclear magnetic resonance relaxation in flexible molecules

Zerbetto

Polimeno

2016

Int J of Quantum Chemistry

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In this tutorial review, we provide a comprehensive description of a multiscale methodology tailored to the calculation of nuclear magnetic resonance (NMR) relaxation data of flexible molecules, based on the definition, parametrization, and solution of a Smoluchowski equation defined for a set of relevant molecular coordinates. While the method is applicable in principle to any collection of internal degrees of freedom, here we focus on flexibility described in terms of torsion angles under the paradigm of what we call the diffusive chain model. The theoretical basis of the multiscale stochastic approach to NMR spectroscopy is provided in detail. Computational aspects are discussed, pointing at a suggested set of specific software packages. To give to this contribution a hands-on component, a self-contained tutorial is made available as Supporting Information with the discussion of some examples taken from recently published studies.diffusive chain model, integrated computational approach, nuclear magnetic resonance, stochastic methods | I N T R O D U C T I O NIn this contribution, we present a general overview of a multiscale modeling approach to the interpretation of spectroscopic observables that are highly sensitive to molecular flexibility. In particular, we discuss a stochastic approach for the calculation of nuclear magnetic resonance (NMR) relaxation data of flexible molecules. In a multiscale spirit, all parameters entering the basic stochastic equation are calculated (or evaluated) using a proper level of description of the molecule, which can be quantum mechanical (QM), classical, or hybrid quantumclassical, depending on the type of the required parameter. After a short general review of the connection between molecular dynamics (MD) and spectroscopic observables, the discussion will be focused on NMR studies of molecules in solution, where the fast motional regime can be invoked.Our target is the description of the structural dynamics of a given flexible molecular system. MD is a fundamental ingredient, together with structural properties, that needs to be taken into account when interpreting, understanding, and predicting both single-molecule and bulk properties of matter. Just to mention a few important examples, dynamics affects proteins properties in a number of different ways, from tuning the binding properties of folded proteins to regulating pathways of folding and binding, from modulating allosteric regulation to controlling function in disordered/unstructured proteins or domains. [1,2] MD is also at the basis of function of molecular machines [3] and it can modulate charge transfer in molecular electronic devices. [4] Having access to molecular motions is, thus, of primary importance and a number of experimental (spectroscopic) techniques are at present available, which are split in two main branches: bulk and single-molecule experiments.NMR is the selected bulk technique to be described in this tutorial review. It is widely used in studying structure and dynamics of biomolecules, es...

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Protein Dynamics by NMR Spin Relaxation: The Slowly Relaxing Local Structure Perspective

Cited by 10 publications

References 71 publications

Analysis of ¹⁵N–¹H NMR Relaxation in Proteins by a Combined Experimental and Molecular Dynamics Simulation Approach: Picosecond–Nanosecond Dynamics of the Rho GTPase Binding Domain of Plexin-B1 in the Dimeric State Indicates Allosteric Pathways

Analysis of ¹⁵N–¹H NMR Relaxation in Proteins by a Combined Experimental and Molecular Dynamics Simulation Approach: Picosecond–Nanosecond Dynamics of the Rho GTPase Binding Domain of Plexin-B1 in the Dimeric State Indicates Allosteric Pathways

Local Ordering at Mobile Sites in Proteins from Nuclear Magnetic Resonance Relaxation: The Role of Site Symmetry

Multiscale modeling for interpreting nuclear magnetic resonance relaxation in flexible molecules

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Protein Dynamics by NMR Spin Relaxation: The Slowly Relaxing Local Structure Perspective

Cited by 10 publications

References 71 publications

Analysis of 15N–1H NMR Relaxation in Proteins by a Combined Experimental and Molecular Dynamics Simulation Approach: Picosecond–Nanosecond Dynamics of the Rho GTPase Binding Domain of Plexin-B1 in the Dimeric State Indicates Allosteric Pathways

Analysis of 15N–1H NMR Relaxation in Proteins by a Combined Experimental and Molecular Dynamics Simulation Approach: Picosecond–Nanosecond Dynamics of the Rho GTPase Binding Domain of Plexin-B1 in the Dimeric State Indicates Allosteric Pathways

Local Ordering at Mobile Sites in Proteins from Nuclear Magnetic Resonance Relaxation: The Role of Site Symmetry

Multiscale modeling for interpreting nuclear magnetic resonance relaxation in flexible molecules

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Analysis of ¹⁵N–¹H NMR Relaxation in Proteins by a Combined Experimental and Molecular Dynamics Simulation Approach: Picosecond–Nanosecond Dynamics of the Rho GTPase Binding Domain of Plexin-B1 in the Dimeric State Indicates Allosteric Pathways

Analysis of ¹⁵N–¹H NMR Relaxation in Proteins by a Combined Experimental and Molecular Dynamics Simulation Approach: Picosecond–Nanosecond Dynamics of the Rho GTPase Binding Domain of Plexin-B1 in the Dimeric State Indicates Allosteric Pathways