Related Articles13C NMR Relaxation Analysis of Protein GB3 for the Assessment of Sidechain Dynamics Predictions by Current AMBER and CHARMM Force Fields.
Abstract
Molecular simulations with seven current AMBER- and CHARMM-based force fields yield markedly differing internal bond vector autocorrelation function predictions for many of the 223 methine and methylene H-C bonds of the 56-residue protein GB3. To enable quantification of accuracy, 13C R1, R2, and heteronuclear NOE relaxation rates have been determined for the methine and stereochemically-assigned methylene C? and C? positions. With only three experimental relaxation values for each bond vector, central to this analysis is the accuracy with which MD-derived autocorrelation curves can be represented by a 3-parameter equation which, in turn, maps onto the NMR relaxation values. In contrast to the more widely used extended Lipari-Szabo order parameter representation, 95% of these MD-derived internal autocorrelation curves for GB3 can be fitted to within 1.0% rmsd over the timeframe from 30 ps to 4 ns by a biexponential Larmor frequency-selective representation (LF-S2). Applying the LF-S2 representation to the experimental relaxation rates and uncertainties serves to determine the boundary range for the autocorrelation function of each bond vector consistent with the experimental data. Not surprisingly, all seven force fields predict the autocorrelation functions for the more motionally-restricted 1H?-13C? and 1H?-13C? bond vectors with reasonable accuracy. However, for the 1H?-13C? bond vectors exhibiting aggregate order parameter S2 values less than 0.85, only 1% of the MD-derived predictions lie with 1 ? of the experimentally determined autocorrelation functions and only 7% within 2 ?. On the other hand, substantial residue type-specific improvements in predictive performance were observed among the recent AMBER force fields. This analysis indicates considerable potential for the use of 13C relaxation measurements in guiding the optimization of the sidechain dynamics characteristics of protein molecular simulations.
PMID: 32268062 [PubMed - as supplied by publisher]
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Abstract
NMR chemical shifts can be computed from molecular dynamics (MD) simulations using a template matching approach and a library of conformers containing chemical shifts generated from ab initio quantum calculations. This approach has potential utility for evaluating the force fields that underlie these simulations....
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07-09-2017 11:44 PM
On the ability of molecular dynamics force fields to recapitulate NMR derived protein side chain order parameters
On the ability of molecular dynamics force fields to recapitulate NMR derived protein side chain order parameters
Abstract
Molecular dynamics (MD) simulations have become a central tool for investigating various biophysical questions with atomistic detail. While many different proxies are used to qualify MD force fields, most are based on largely structural parameters such as the root mean square deviation from experimental coordinates or nuclear magnetic resonance (NMR) chemical shifts and residual dipolar couplings. NMR derived Lipari–Szabo squared generalized order parameter (O2)...
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[NMR paper] On the ability of molecular dynamics force fields to recapitulate NMR derived protein side chain NMR order parameters.
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Protein Sci. 2016 Mar 14;
Authors: O'Brien ES, Wand AJ, Sharp KA
Abstract
Molecular dynamics (MD) simulations have become a central tool for investigating various biophysical questions with atomistic detail. While many different proxies are used to qualify molecular dynamics force fields, most...
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03-19-2016 09:23 PM
On the ability of molecular dynamics force fields to recapitulate NMR derived protein side chain NMR order parameters
On the ability of molecular dynamics force fields to recapitulate NMR derived protein side chain NMR order parameters
Abstract
Molecular dynamics (MD) simulations have become a central tool for investigating various biophysical questions with atomistic detail. While many different proxies are used to qualify molecular dynamics force fields, most are based on largely structural parameters such as the root mean square deviation from experimental coordinates or NMR chemical shifts and residual dipolar couplings. NMR derived Lipari-Szabo squared generalized order parameter (O2) values of...
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Authors: Best RB, Zhu X, Shim J, Lopes PE, Mittal J, Feig M, Mackerell AD
Abstract
While the quality of the current CHARMM22/CMAP additive force field for...
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Chemical shift prediction for protein structure calculation and quality assessment using an optimally parameterized force field
Chemical shift prediction for protein structure calculation and quality assessment using an optimally parameterized force field
Publication year: 2011
Source: Progress in Nuclear Magnetic Resonance Spectroscopy, In Press, Accepted Manuscript, Available online 23 May 2011</br>
Jakob T., Nielsen , Hamid R., Eghbalnia , Niels Chr., Nielsen</br>
The exquisite sensitivity of chemical shifts as reporters of structural information, and the ability to measure them routinely and accurately, gives great import to formulations that elucidate the structure-chemical-shift relationship. Here we...
13C NMR Relaxation Analysis of Protein GB3 for the Assessment of Sidechain Dynamics Predictions by Current AMBER and CHARMM Force Fields.
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