Rotational velocity rescaling of molecular dynamics trajectories for direct prediction of protein NMR relaxation

Anderson, Janet S.; LeMaster, David M.

doi:10.1016/j.bpc.2012.05.005

“…Assuming an 15 N CSA value of 168 ppm (Anderson and LeMaster 2012) and a 1 H- 15 N bond length of 1.020 Å, this difference equals 0.18 (0.44-0.26) for B′ at 900 MHz and B′′ at 600 MHz, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…Under the assumption of no exchange linebroadening, the difference between R 2 -R 1 /2 measurements (O) scaled between two different magnetic field strengths (600 and 900 1 H) have been used to calculate Δ 15 N CSA according to Eq. 6, assuming a mean CSA anisotropy value of 168 ppm (Anderson and LeMaster 2012) and a 1 H- 15 N bond length of 1.02 Å.…”

Section: Figmentioning

confidence: 99%

Quantifying protein dynamics in the ps–ns time regime by NMR relaxation

Hernández

¹

,

LeMaster

²

2016

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Both 15N chemical shift anisotropy (CSA) and sufficiently rapid exchange linebroadening transitions exhibit relaxation contributions that are proportional to the square of the magnetic field. Deconvoluting these contributions is further complicated by residue-dependent variations in protein amide 15N CSA values which have proven difficult to accurately measure. Exploiting recently reported improvements for the implementation of T1 and T1ρ experiments, field strength-dependent studies have been carried out on the B3 domain of protein G (GB3) as well as on the immunophilin FKBP12 and a H87V variant of that protein in which the major conformational exchange linebroadening transition is suppressed. By applying a zero frequency spectral density rescaling analysis to the relaxation data collected at magnetic fields from 500 MHz 1H to 900 MHz 1H, differential residue-specific 15N CSA values have been obtained for GB3 which correlate with those derived from solid state and liquid crystalline NMR measurements to a level similar to the correlation among those previously reported studies. Application of this analysis protocol to FKBP12 demonstrated an efficient quantitation of both weak exchange linebroadening contributions and differential residue-specific 15N CSA values. Experimental access to such differential residue-specific 15N CSA values should significantly facilitate more accurate comparisons with molecular dynamics simulations of protein motion that occurs within the timeframe of global molecular tumbling.

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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%

“…done by Anderson and coworkers. 65,66 In the same vein, to investigate the influence of the overall tumbling in the CHARMM36/TIP3P simulations, we rescaled the rotational diffusion time for computing C O (t) via eq 11 by a factor of 2.73, which corresponds to the ratio of the rotational diffusion constants obtained in TIP3P water and TIP4P-2005 water ( Table 3).…”

Section: Backbone Relaxationmentioning

confidence: 99%

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

Hoffmann¹,

Mulder²,

Schäfer³

2019

Preprint

0

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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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“…The time scale of rotational diffusion in MD simulations strongly depends on the water model. 16,44,61,[67][68][69][70] While the water model usually does not have a strong effect on the internal dynamics of backbone N-H bonds, it changes the time scale of overall rotational tumbling and therefore the spectral densities. Table 3 Overall tumbling of the protein is slow compared to most of its internal dynamics and mainly affects spectral densities at low frequencies.…”

Section: Rotational Diffusionmentioning

confidence: 99%

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

Hoffmann

¹

,

Mulder²,

Schäfer³

2019

Preprint

0

View full text Add to dashboard Cite

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 velocity rescaling of molecular dynamics trajectories for direct prediction of protein NMR relaxation

Cited by 20 publications

References 46 publications

Quantifying protein dynamics in the ps–ns time regime by NMR relaxation

Quantifying protein dynamics in the ps–ns time regime by NMR relaxation

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

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

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