Protein Dielectric Constants Determined from NMR Chemical Shift Perturbations.
J Am Chem Soc. 2013 Oct 14;
Authors: Kukic P, Farrell D, McIntosh LP, Garcia-Moreno E B, Jensen KS, Toleikis Z, Teilum K, Nielsen JE
Abstract
Understanding the connection between protein structure and function requires a quantitative understanding of electrostatic effects. Structure-based electrostatics calculations are essential for this purpose, but their use have been limited by a long-standing discussion on which value to use for the dielectric constants (?eff and ?p) required in Coulombic models and Poisson-Boltzmann models. The currently used values for ?eff and ?p are essentially empirical parameters calibrated against thermo-dynamic properties that are indirect measurements of protein electric fields. We determine optimal values for ?eff and ?p by measuring protein electric fields in solution using direct detection of NMR chemical shift perturbations (CSPs). We measured CSPs in fourteen proteins to get a broad and general characterization of electric fields. Coulomb's law reproduces the measured CSPs optimally with a protein dielectric constant (?eff) from 3 to 13, with an optimal value across all proteins of 6.5. However, when the water-protein interface is treated with finite difference Poisson-Boltzmann calculations, the optimal protein dielectric constant (?p) rangedsfrom 2-5 with an optimum of 3. It is striking how similar this value is to the dielectric constant of 2-4 meas-ured for protein powders, and how different it is from the ?p of 6-20 used in models based on the Poisson-Boltzmann equation when calculating thermodynamic parameters. Because the value of ?p = 3 is obtained by analysis of NMR chemical shift perturba-tions instead of thermodynamic parameters such as pKa values, it is likely to describe only the electric field and thus represent a more general, intrinsic, and transferable ?p common to most folded proteins.
PMID: 24124752 [PubMed - as supplied by publisher]
[NMR paper] Practical use of chemical shift databases for protein solid-state NMR: 2D chemical shift maps and amino-acid assignment with secondary-structure information.
Practical use of chemical shift databases for protein solid-state NMR: 2D chemical shift maps and amino-acid assignment with secondary-structure information.
Practical use of chemical shift databases for protein solid-state NMR: 2D chemical shift maps and amino-acid assignment with secondary-structure information.
J Biomol NMR. 2013 Apr 28;
Authors: Fritzsching KJ, Yang Y, Schmidt-Rohr K, Hong M
Abstract
We introduce a Python-based program that utilizes the large database of (13)C and (15)N chemical shifts in the Biological Magnetic...
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[NMR paper] NightShift: NMR Shift Inference by General Hybrid Model Training - a Framework for NMR Chemical Shift Prediction.
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Related Articles NightShift: NMR Shift Inference by General Hybrid Model Training - a Framework for NMR Chemical Shift Prediction.
BMC Bioinformatics. 2013 Mar 16;14(1):98
Authors: Dehof AK, Loew S, Lenhof HP, Hildebrandt A
Abstract
NMR chemical shift prediction plays an important role in various applications in computational biology. Among others, structure determination, structure optimization, and the scoring of docking...
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03-19-2013 01:22 PM
Accuracy and precision of proteinâ??ligand interaction kinetics determined from chemical shift titrations
Accuracy and precision of proteinâ??ligand interaction kinetics determined from chemical shift titrations
Abstract NMR-monitored chemical shift titrations for the study of weak proteinâ??ligand interactions represent a rich source of information regarding thermodynamic parameters such as dissociation constants (K D ) in the micro- to millimolar range, populations for the free and ligand-bound states, and the kinetics of interconversion between states, which are typically within the fast exchange regime on the NMR timescale. We recently developed two chemical shift titration methods...
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10-24-2012 10:28 PM
Increased precision for analysis of proteinâ??ligand dissociation constants determined from chemical shift titrations
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Abstract NMR is ideally suited for the analysis of proteinâ??protein and protein ligand interactions with dissociation constants ranging from ~2 ÎĽM to ~1 mM, and with kinetics in the fast exchange regime on the NMR timescale. For the determination of dissociation constants (K D ) of 1:1 proteinâ??protein or proteinâ??ligand interactions using NMR, the protein and ligand concentrations must necessarily be similar in magnitude to the K D , and nonlinear least squares...
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05-01-2012 07:06 AM
Interpreting protein chemical shift data
Interpreting protein chemical shift data
Publication year: 2011
Source:Progress in Nuclear Magnetic Resonance Spectroscopy, Volume 58, Issues 1–2</br>
David S. Wishart</br>
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03-09-2012 09:16 AM
SHIFTCOR: Protein Chemical Shift Re-referencing
SHIFTCOR website
SHIFTCOR is an automated shift correction program that uses statistical methods to compare and correct SHIFTX-predicted shifts relative to an input set of observed chemical shifts. SHIFTCOR uses several simple statistical approaches and pre-determined cutoff values to identify and correct potential referencing, assignment and typographical errors. SHIFTCOR identifies potential chemical shift referencing problems by comparing the difference between the average value of each set (1Hα, 13Cα, 13Cβ, 13CO, 15N and 1HN) of observed and predicted chemical shifts. The difference...
gwnmr
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01-10-2012 06:46 PM
Local protein backbone folds determined by calculated NMR chemical shifts.
Local protein backbone folds determined by calculated NMR chemical shifts.
Local protein backbone folds determined by calculated NMR chemical shifts.
J Comput Chem. 2011 Sep 9;
Authors: Czajlik A, Hudáky I, Perczel A
Abstract
NMR chemical shifts (CSs: ?N(NH) , ?C(?) , ?C(?) , ?C', ?H(NH) , and ?H(?) ) were computed for the amino acid backbone conformers (?(L) , ?(L) , ?(L) , ?(L) , ?(L) , ?(D) , ?(D) , ?(D) , and ?(D) ) modeled by oligoalanine structures. Topological differences of the extended fold were investigated on single ?-strands,...
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09-10-2011 06:51 PM
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http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www3.interscience.wiley.com-aboutus-images-wiley_interscience_pubmed_logo_FREE_120x27.gif http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.pubmedcentral.nih.gov-corehtml-pmc-pmcgifs-pubmed-pmc.gif Related Articles Demonstration of protein-protein interaction specificity by NMR chemical shift mapping.
Protein Sci. 1997 Dec;6(12):2624-7
Authors: Rajagopal P, Waygood EB, Reizer J, Saier MH, Klevit RE
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Protein Dielectric Constants Determined from NMR Chemical Shift Perturbations.
Linear Mode
