Local isotropic diffusion approximation for coupled internal and overall molecular motions in NMR spin relaxation.
Ontology highlight
ABSTRACT:
SUBMITTER: Gill ML
PROVIDER: S-EPMC4174990 | biostudies-literature | 2014 Sep
REPOSITORIES: biostudies-literature
Publications
Local isotropic diffusion approximation for coupled internal and overall molecular motions in NMR spin relaxation.
Gill Michelle L ML Palmer Arthur G AG
The journal of physical chemistry. B 20140911 38
The present work demonstrates that NMR spin relaxation rate constants for molecules interconverting between states with different diffusion tensors can be modeled theoretically by combining orientational correlation functions for exchanging spherical molecules with locally isotropic approximations for the diffusion anisotropic tensors. The resulting expressions are validated by comparison with correlation functions obtained by Monte Carlo simulations and are accurate for moderate degrees of diff ...[more]
Similar Datasets
Project description:Calculating NMR relaxation effects for proteins with dynamics on multiple time scales generally requires very long trajectories based on conventional molecular dynamics simulations. In this report, we have built Markov state models from multiple MD trajectories and used the resulting MSM to capture the very fast internal motions of the protein within a free energy basin on a time scale up to hundreds of picoseconds and the more than 3 orders of magnitude slower conformational exchange between macrostates. To interpret the relaxation data, we derive new equations using the model-free framework which includes two slowly exchanging macrostates, each of which also exhibits fast local motions. Using simulations of HIV-1 protease as an example, we show how the populations of slowly exchanging conformational states as well as order parameters for the different states can be determined from the NMR relaxation data.
| S-EPMC3727231 | biostudies-literature
Project description:The three-dimensional structures of macromolecules fluctuate over a wide range of time-scales. Separating the individual dynamic processes according to frequency is of importance in relating protein motions to biological function and stability. We present here a general NMR method for the specific characterization of microsecond motions at backbone positions in proteins even in the presence of other dynamics such as large-amplitude nanosecond motions and millisecond chemical exchange processes. The method is based on measurement of relaxation rates of four bilinear coherences and relies on the ability of strong continuous radio frequency fields to quench millisecond chemical exchange. The utility of the methodology is demonstrated and validated through two specific examples focusing on the thermo-stable proteins, ubiquitin and protein L, where it is found that small-amplitude microsecond dynamics are more pervasive than previously thought. Specifically, these motions are localized to alpha helices, loop regions, and regions along the rim of beta sheets in both of the proteins examined. A third example focuses on a 28 kDa ternary complex of the chaperone Chz1 and the histones H2A.Z/H2B, where it is established that pervasive microsecond motions are localized to a region of the chaperone that is important for stabilizing the complex. It is further shown that these motions can be well separated from extensive millisecond dynamics that are also present and that derive from exchange of Chz1 between bound and free states. The methodology is straightforward to implement, and data recorded at only a single static magnetic field are required.
| S-EPMC7386800 | biostudies-literature
Project description:The measurement of long-range distances remains a challenge in solid-state NMR structure determination of biological macromolecules. In 2D and 3D correlation spectra of uniformly (13)C-labeled biomolecules, inter-residue, inter-segmental, and intermolecular (13)C-(13)C cross peaks that provide important long-range distance constraints for three-dimensional structures often overlap with short-range cross peaks that only reflect the covalent structure of the molecule. It is therefore desirable to develop new approaches to obtain spectra containing only long-range cross peaks. Here we show that a relaxation-compensated modification of the commonly used 2D (1)H-driven spin diffusion (PDSD) experiment allows the clean detection of such long-range cross peaks. By adding a z-filter to keep the total z-period of the experiment constant, we compensate for (13)C T1 relaxation. As a result, the difference spectrum between a long- and a scaled short-mixing time spectrum show only long-range correlation signals. We show that one- and two-bond cross peaks equalize within a few tens of milliseconds. Within ~200 ms, the intensity equilibrates within an amino acid residue and a monosaccharide to a value that reflects the number of spins in the local network. With T1 relaxation compensation, at longer mixing times, inter-residue and inter-segmental cross peaks increase in intensity whereas intra-segmental cross-peak intensities remain unchanged relative to each other and can all be subtracted out. Without relaxation compensation, the difference 2D spectra exhibit both negative and positive intensities due to heterogeneous T1 relaxation in most biomolecules, which can cause peak cancellation. We demonstrate this relaxation-compensated difference PDSD approach on amino acids, monosaccharides, a crystalline model peptide, a membrane-bound peptide and a plant cell wall sample. The resulting difference spectra yield clean multi-bond, inter-residue and intermolecular correlation peaks, which are often difficult to resolve in the parent 2D spectra.
| S-EPMC4522165 | biostudies-literature
Project description:Intrinsically disordered proteins and intrinsically disordered regions (IDRs) are ubiquitous in the eukaryotic proteome. The description and understanding of their conformational properties require the development of new experimental, computational, and theoretical approaches. Here, we use nuclear spin relaxation to investigate the distribution of timescales of motions in an IDR from picoseconds to nanoseconds. Nitrogen-15 relaxation rates have been measured at five magnetic fields, ranging from 9.4 to 23.5 T (400-1000 MHz for protons). This exceptional wealth of data allowed us to map the spectral density function for the motions of backbone NH pairs in the partially disordered transcription factor Engrailed at 11 different frequencies. We introduce an approach called interpretation of motions by a projection onto an array of correlation times (IMPACT), which focuses on an array of six correlation times with intervals that are equidistant on a logarithmic scale between 21 ps and 21 ns. The distribution of motions in Engrailed varies smoothly along the protein sequence and is multimodal for most residues, with a prevalence of motions around 1 ns in the IDR. We show that IMPACT often provides better quantitative agreement with experimental data than conventional model-free or extended model-free analyses with two or three correlation times. We introduce a graphical representation that offers a convenient platform for a qualitative discussion of dynamics. Even when relaxation data are only acquired at three magnetic fields that are readily accessible, the IMPACT analysis gives a satisfactory characterization of spectral density functions, thus opening the way to a broad use of this approach.
| S-EPMC4564687 | biostudies-literature
Project description:The backbone dynamics and overall tumbling of protein G have been investigated using 15N relaxation. Comparison of measured R2/R1 relaxation rate ratios with known three-dimensional coordinates of the protein show that the rotational diffusion tensor is significantly asymmetric, exhibiting a prolate axial symmetry. Extensive Monte Carlo simulations have been used to estimate the uncertainty due to experimental error in the relaxation rates to be D(parallel)/D(perpendicular) = 1.68 +/- 0.08, while the dispersion in the NMR ensemble leads to a variation of D(parallel)/D(perpendicular) = 1.65 +/- 0.03. Incorporation of this tensorial description into a Lipari-Szabo type analysis of internal motion has allowed us to accurately describe the local dynamics of the molecule. This analysis differs from an earlier study where the overall rotational diffusion was described by a spherical top. In this previous analysis, exchange parameters were fitted to many of the residues in the alpha helix. This was interpreted as reflecting a small motion of the alpha helix with respect to the beta sheet. We propose that the differential relaxation properties of this helix compared to the beta sheet are due to the near-orthogonality of the NH vectors in the two structural motifs with respect to the unique axis of the diffusion tensor. Our analysis shows that when anisotropic rotational diffusion is taken into account NH vectors in these structural motifs appear to be equally rigid. This study underlines the importance of a correct description of the rotational diffusion tensor if internal motion is to be accurately investigated.
| S-EPMC2144651 | biostudies-other
Project description:Understanding the effects of spin-orbit coupling (SOC) and many-body interactions on spin transport is important in condensed matter physics and spintronics. This topic has been intensively studied for spin carriers such as electrons but barely explored for charge-neutral bosonic quasiparticles (including their condensates), which hold promises for coherent spin transport over macroscopic distances. Here, we explore the effects of synthetic SOC (induced by optical Raman coupling) and atomic interactions on the spin transport in an atomic Bose-Einstein condensate (BEC), where the spin-dipole mode (SDM, actuated by quenching the Raman coupling) of two interacting spin components constitutes an alternating spin current. We experimentally observe that SOC significantly enhances the SDM damping while reducing the thermalization (the reduction of the condensate fraction). We also observe generation of BEC collective excitations such as shape oscillations. Our theory reveals that the SOC-modified interference, immiscibility, and interaction between the spin components can play crucial roles in spin transport.
| S-EPMC6343014 | biostudies-literature
Project description:For many pathologies, early structural tissue changes occur at the cellular level, on the scale of micrometers or tens of micrometers. Magnetic resonance imaging (MRI) is a powerful non-invasive imaging tool used for medical diagnosis, but its clinical hardware is incapable of reaching the cellular length scale directly. In spite of this limitation, microscopic tissue changes in pathology can potentially be captured indirectly, from macroscopic imaging characteristics, by studying water diffusion. Here we focus on water diffusion and NMR relaxation in the human prostate, a highly heterogeneous organ at the cellular level. We present a physical picture of water diffusion and NMR relaxation in the prostate tissue, that is comprised of a densely-packed cellular compartment (composed of stroma and epithelium), and a luminal compartment with almost unrestricted water diffusion. Transverse NMR relaxation is used to identify fast and slow T 2 components, corresponding to these tissue compartments, and to disentangle the luminal and cellular compartment contributions to the temporal evolution of the overall water diffusion coefficient. Diffusion in the luminal compartment falls into the short-time surface-to-volume (S/V) limit, indicating that only a small fraction of water molecules has time to encounter the luminal walls of healthy tissue; from the S/V ratio, the average lumen diameter averaged over three young healthy subjects is measured to be 217.7±188.7 ?m. Conversely, the diffusion in the cellular compartment is highly restricted and anisotropic, consistent with the fibrous character of the stromal tissue. Diffusion transverse to these fibers is well described by the random permeable barrier model (RPBM), as confirmed by the dynamical exponent ? = 1/2 for approaching the long-time limit of diffusion, and the corresponding structural exponent p = -1 in histology. The RPBM-derived fiber diameter and membrane permeability were 19.8±8.1 ?m and 0.044±0.045 ?m/ms, respectively, in agreement with known values from tissue histology and membrane biophysics. Lastly, we revisited 38 prostate cancer cases from a recently published study, and found the same dynamical exponent ? = 1/2 of diffusion in tumors and benign regions. Our results suggest that a multi-parametric MRI acquisition combined with biophysical modeling may be a powerful non-invasive complement to prostate cancer grading, potentially foregoing biopsies.
| S-EPMC6296484 | biostudies-literature
Project description:Clays, hydrous aluminous phyllosilicates, have a significant impact on the interpretation of physical measurements and properties of porous media. In particular, the presence of paramagnetic and/or ferromagnetic ions like iron, nickel, and magnesium in clays can complicate the analysis of nuclear magnetic resonance (NMR) data for porous media characterization. This is due to the internal magnetic field gradient induced by the clay minerals. In this study, we aim to investigate the impact of clay content on spin-spin relaxation time (T 2), which is strongly influenced by the pore surface chemistry. Seven rock core plugs, characterized with variable clay content, were used for this purpose. The clay mineralogy and volume were determined by means of quantitative evaluation of minerals by scanning electron microscopy (QEMSCAN). The T 2 relaxation time was measured using a Carr-Purcell-Meiboom-Gill (CPMG) sequence with variable echo spacing (T E). The maximum percentage difference in dominant T 2 values (MRDT 2) between shortest and longest echo spacing was subsequently correlated with clay content obtained from QEMSCAN. Our results show that the reduction in T 2 distribution with increasing echo time T E is more significant in samples characterized by higher clay contents. The MRDT 2 was found to be strongly correlated with clay content. An analytical equation is presented expressing MRDT 2 as a function of clay content providing a quick and non-destructive approach for clay content estimation. Moreover, the MRDT 2-clay content relationship showed a nonlinear behavior: MRDT 2 increases drastically as the clay content increases up to 15%, beyond which the rate of MRDT 2 change with clay content diminishes. This behavior could be attributed to the clay distribution. At higher clay contents (above 15%), it is more likely for clay to form clusters (structural clays), which will not significantly increase the clay surface in contact with the pore fluid. Further, experimental data suggests that ignoring the impact of clay on internal magnetic gradients and T 2 signal may result in considerable underestimation of the actual pore size distribution.
| S-EPMC7114610 | biostudies-literature
Project description:PurposeTo perform in vivo isotropic-resolution diffusion tensor imaging (DTI) of lumbosacral and sciatic nerves with a phase-navigated diffusion-prepared (DP) 3D turbo spin echo (TSE) acquisition and modified reconstruction incorporating intershot phase-error correction and to investigate the improvement on image quality and diffusion quantification with the proposed phase correction.MethodsPhase-navigated DP 3D TSE included magnitude stabilizers to minimize motion and eddy-current effects on the signal magnitude. Phase navigation of motion-induced phase errors was introduced before readout in 3D TSE. DTI of lower back nerves was performed in vivo using 3D TSE and single-shot echo planar imaging (ss-EPI) in 13 subjects. Diffusion data were phase-corrected per kz plane with respect to T2 -weighted data. The effects of motion-induced phase errors on DTI quantification was assessed for 3D TSE and compared with ss-EPI.ResultsNon-phase-corrected 3D TSE resulted in artifacts in diffusion-weighted images and overestimated DTI parameters in the sciatic nerve (mean diffusivity [MD]?=?2.06?±?0.45). Phase correction of 3D TSE DTI data resulted in reductions in all DTI parameters (MD?=?1.73?±?0.26) of statistical significance (P???0.001) and in closer agreement with ss-EPI DTI parameters (MD?=?1.62?±?0.21).ConclusionDP 3D TSE with phase correction allows distortion-free isotropic diffusion imaging of lower back nerves with robustness to motion-induced artifacts and DTI quantification errors. Magn Reson Med 80:609-618, 2018. © 2018 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
| S-EPMC5947302 | biostudies-literature
Project description:A new computational strategy is reported that provides a fast approximation of numerical solutions of differential equations in general. The method is demonstrated with the analysis of NMR adiabatic relaxation dispersion experiments to reveal biomolecular dynamics. When an analytical solution to the theoretical equations describing a physical process is not available, the new approach can significantly accelerate the computational speed of the conventional numerical integration up to 10(5) times. NMR adiabatic relaxation dispersion experiments enhanced with optimized proton-decoupled pulse sequences, although extremely powerful, have previously been refractory to quantitative analysis. Both simulations and experimental validation demonstrate detectable "slow" (microsecond to millisecond) conformational exchange rates from 10(2) to 10(5) s(-1). This greatly expanded time-scale range enables the characterization of a wide array of conformational fluctuations for individual residues, which correlate with biomolecular function and were previously inaccessible. Moreover, the new computational method can be potentially generalized for analysis of new types of relaxation dispersion experiments to characterize the various dynamics of biomolecular systems.
| S-EPMC6344943 | biostudies-literature