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) values of amide NH bond vectors of the polypeptide chain were also often employed for refinement and validation. However, with a few exceptions, side chain methyl symmetry axis order parameters have not been incorporated into experimental reference sets. Using a test set of five diverse proteins, the performance of several force fields implemented in the NAMDD simulation package was examined. It was found that simulations employing explicit water implemented using the TIP3 model generally performed significantly better than those using implicit water in reproducing experimental methyl symmetry axis O2 values. Overall the CHARMM27 force field performs nominally better than two implementations of the Amber force field. It appeared that recent quantum mechanics modifications to side chain torsional angles of leucine and isoleucine in the Amber force field have significantly hindered proper motional modeling for these residues. There remained significant room for improvement as even the best correlations of experimental and simulated methyl group Lipari–Szabo generalized order parameters fall below an R2 of 0.8.
[NMR paper] 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.
On the ability of molecular dynamics force fields to recapitulate NMR derived protein side chain NMR order parameters.
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...
nmrlearner
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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...
nmrlearner
Journal club
0
03-15-2016 11:57 AM
[NMR paper] On the relationship between NMR-derived amide order parameters and protein backbone entropy changes.
On the relationship between NMR-derived amide order parameters and protein backbone entropy changes.
Related Articles On the relationship between NMR-derived amide order parameters and protein backbone entropy changes.
Proteins. 2015 Mar 4;
Authors: Sharp KA, O'Brien E, Kasinath V, Wand AJ
Abstract
Molecular dynamics simulations are used to analyze the relationship between NMR-derived squared generalized order parameters of amide NH groups and backbone entropy. Amide order parameters (O(2) NH ) are largely determined by the...
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03-06-2015 02:01 PM
[NMR paper] Banding of NMR-derived methyl order parameters: Implications for protein dynamics.
Banding of NMR-derived methyl order parameters: Implications for protein dynamics.
Related Articles Banding of NMR-derived methyl order parameters: Implications for protein dynamics.
Proteins. 2014 Mar 26;
Authors: Sharp KA, Kasinath V, Wand AJ
Abstract
Our understanding of protein folding, stability and function has begun to more explicitly incorporate dynamical aspects. Nuclear magnetic resonance has emerged as a powerful experimental method for obtaining comprehensive site-resolved insight into protein motion. It has been observed that...
[NMR paper] Temperature dependence of NMR order parameters and protein dynamics.
Temperature dependence of NMR order parameters and protein dynamics.
Related Articles Temperature dependence of NMR order parameters and protein dynamics.
J Am Chem Soc. 2003 Sep 17;125(37):11158-9
Authors: Massi F, Palmer AG
The helical subdomain, HP36, of the F-actin-binding headpiece domain of chicken villin, is the smallest naturally occurring polypeptide that folds to a thermostable compact structure. Unconstrained molecular dynamics simulations and constrained molecular dynamics simulations using umbrella sampling are used to study the...
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11-24-2010 09:16 PM
[NMR paper] Correlation between 2H NMR side-chain order parameters and sequence conservation in g
Correlation between 2H NMR side-chain order parameters and sequence conservation in globular proteins.
Related Articles Correlation between 2H NMR side-chain order parameters and sequence conservation in globular proteins.
J Am Chem Soc. 2003 Jul 30;125(30):9004-5
Authors: Mittermaier A, Davidson AR, Kay LE
Side-chain 2H NMR relaxation data have been collected for the SH3 domain from the Fyn tyrosine kinase and analyzed with respect to sequence preference and per-residue solvent accessibility. Residues that are highly preferred at a given...
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11-24-2010 09:16 PM
[NMR paper] Protein dynamics using frequency-dependent order parameters from analysis of NMR rela
Protein dynamics using frequency-dependent order parameters from analysis of NMR relaxation data.
Related Articles Protein dynamics using frequency-dependent order parameters from analysis of NMR relaxation data.
J Magn Reson. 2003 Mar;161(1):118-25
Authors: Idiyatullin D, Daragan VA, Mayo KH
A novel approach is described to analyze NMR relaxation data on proteins. This method introduces the frequency-dependent order parameter, S(2)(omega), in order to estimate contributions to the generalized order parameter S(2) from different motional...
On the ability of molecular dynamics force fields to recapitulate NMR derived protein side chain order parameters
H bond vectors of the polypeptide chain were also often employed for refinement and validation. However, with a few exceptions, side chain methyl symmetry axis order parameters have not been incorporated into experimental reference sets. Using a test set of five diverse proteins, the performance of several force fields implemented in the NAMDD simulation package was examined. It was found that simulations employing explicit water implemented using the TIP3 model generally performed significantly better than those using implicit water in reproducing experimental methyl symmetry axis O2 values. Overall the CHARMM27 force field performs nominally better than two implementations of the Amber force field. It appeared that recent quantum mechanics modifications to side chain torsional angles of leucine and isoleucine in the Amber force field have significantly hindered proper motional modeling for these residues. There remained significant room for improvement as even the best correlations of experimental and simulated methyl group Lipari–Szabo generalized order parameters fall below an R2 of 0.8.
Linear Mode
