Rotational Dynamics of Proteins from Spin Relaxation Times and Molecular Dynamics Simulations

Ollila, O. H. Samuli; Heikkinen, Hanna; Iwaï, Hideo

doi:10.1021/acs.jpcb.8b02250

Cited by 39 publications

(69 citation statements)

References 70 publications

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“…Before the spin relaxation time calculation, the overestimated overall rotational diffusion in the MD simulation due to the water model was corrected by dividing the rotational diffusion coefficients around all inertia axes with a factor of 1.2, assuming that the protein rotates as an anisotropic rigid body. This scaling factor was found to be capable of reproducing the 15 N spin relaxation times in good agreement with the experimental data of Pa TonB-96 for tip4p water model (Ollila, Heikkinen & Iwaï, 2018). The computer codes used for the analysis and the related data are available (Ollila, 2018b, 2018c).…”

Section: Methodssupporting

confidence: 75%

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NMR structure of the C-terminal domain of TonB protein from Pseudomonas aeruginosa

Oeemig

Ollila

Iwaï

2018

PeerJ

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The TonB protein plays an essential role in the energy transduction system to drive active transport across the outer membrane (OM) using the proton-motive force of the cytoplasmic membrane of Gram-negative bacteria. The C-terminal domain (CTD) of TonB protein is known to interact with the conserved TonB box motif of TonB-dependent OM transporters, which likely induces structural changes in the OM transporters. Several distinct conformations of differently dissected CTDs of Escherichia coli TonB have been previously reported. Here we determined the solution NMR structure of a 96-residue fragment of Pseudomonas aeruginosa TonB (PaTonB-96). The structure shows a monomeric structure with the flexible C-terminal region (residues 338–342), different from the NMR structure of E. coli TonB (EcTonB-137). The extended and flexible C-terminal residues are confirmed by 15N relaxation analysis and molecular dynamics simulation. We created models for the PaTonB-96/TonB box interaction and propose that the internal fluctuations of PaTonB-96 makes it more accessible for the interactions with the TonB box and possibly plays a role in disrupting the plug domain of the TonB-dependent OM transporters.

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Section: Methodssupporting

confidence: 75%

“…Here, we characterize the structural dynamics of Pa TonB-96 by combining T 1 , T 2 , and heteronuclear NOEs for backbone 15 N atoms and MD simulations (Ollila, Heikkinen & Iwaï, 2018). The measured spin relaxation times for Pa TonB-96 are shown together with the MD simulation results (Fig.…”

Section: Resultsmentioning

confidence: 99%

NMR structure of the C-terminal domain of TonB protein from Pseudomonas aeruginosa

Oeemig

Ollila

Iwaï

2018

PeerJ

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“…The temperature in these experiments was 298 K. The T 1 and T 2 relaxation data were processed and analyzed using Bruker Dynamic Center software (version 2.5.5) and the NOE relaxation times were processed and analyzed using CcpNmr Analysis software (version 2.4.2) (Vranken et al, 2005). The approximate time-scales for the CTD rotation were estimated, minimizing the equation (11) from Ollila et al (2018) with respect to the experimentally measured T 1 /T 2 ratios as originally proposed by Kay et al (1989).…”

Section: Backbone Dynamics Of Hptonbmentioning

confidence: 99%

NMR Structure and Dynamics of TonB Investigated by Scar-Less Segmental Isotopic Labeling Using a Salt-Inducible Split Intein

et al. 2020

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The growing understanding of partially unfolded proteins increasingly points to their biological relevance in allosteric regulation, complex formation, and protein design. However, the structural characterization of disordered proteins remains challenging. NMR methods can access both the dynamics and structures of such proteins, yet suffering from a high degeneracy of NMR signals. Here, we overcame this bottleneck utilizing a salt-inducible split intein to produce segmentally isotope-labeled samples with the native sequence, including the ligation junction. With this technique, we investigated the NMR structure and conformational dynamics of TonB from Helicobacter pylori in the presence of a proline-rich low complexity region. Spin relaxation experiments suggest that the several nano-second time scale dynamics of the C-terminal domain (CTD) is almost independent of the faster pico-to-nanosecond dynamics of the low complexity central region (LCCR). Our results demonstrate the utility of segmental isotopic labeling for proteins with heterogenous dynamics such as TonB and could advance NMR studies of other partially unfolded proteins.

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“…The time scale of rotational diffusion in MD simulations strongly depends on the water model. 15,56,62,[64][65][66][67] While the water model usually does not have a strong effect on the dynamics of backbone N-H bonds, it changes the time scale of overall rotational tumbling and therefore the spectral densities. Table 3 summarizes the rotational diffusion constants D iso obtained from our simulations with the different water models.…”

Section: Rotational Diffusionmentioning

confidence: 99%

Predicting NMR Relaxation of Proteins from Molecular Dynamics Simulations with Accurate Methyl Rotation Barriers

Hoffmann¹,

Mulder²,

Schäfer³

2019

Preprint

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The internal dynamics of proteins occurring on time scales from picoseconds to nanoseconds can be sensitively probed by nuclear magnetic resonance (NMR) spin relaxation experiments, as well as by molecular dynamics (MD) simulations. This complementarity oﬀers unique opportunities, provided that the two methods are compared at a suitable level. Recently, several groups have used MD simulations to compute the spectral density of backbone and side-chain molecular motions, and to predict NMR relaxation rates from these. Unfortunately, in the case of methyl groups in protein side-chains, inaccurate energy barriers to methyl rotation were responsible for a systematic discrepancy in the computed relaxation rates, as demonstrated for the AMBER ﬀ99SB*-ILDN force ﬁeld (and related parameter sets), impairing quantitative agreement between simulations and experiments. However, correspondence could be regained by emending the MD force ﬁeld with accurate coupled cluster quantum chemical calculations. Spurred by this positive result, we tested whether this approach could be generally applicable, in spite of the fact that diﬀerent MD force ﬁelds employ diﬀerent water models. Improved methyl group rotation barriers for the CHARMM36 and AMBER ﬀ15ipq protein force ﬁelds were derived, such that the NMR relaxation data obtained from the MD simulations now also display very good agreement with experiment. Results herein showcase the performance of present-day MD force ﬁelds, and manifest their reﬁned ability to accurately describe internal protein dynamics.

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Rotational Dynamics of Proteins from Spin Relaxation Times and Molecular Dynamics Simulations

Cited by 39 publications

References 70 publications

NMR structure of the C-terminal domain of TonB protein from Pseudomonas aeruginosa

NMR structure of the C-terminal domain of TonB protein from Pseudomonas aeruginosa

NMR Structure and Dynamics of TonB Investigated by Scar-Less Segmental Isotopic Labeling Using a Salt-Inducible Split Intein

Predicting NMR Relaxation of Proteins from Molecular Dynamics Simulations with Accurate Methyl Rotation Barriers

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