Quantifying Lipari–Szabo modelfree parameters from 13CO NMR relaxation experiments

Wang, Tianzhi; Weaver, Daniel S.; Cai, Shuqun; Zuiderweg, Erik R. P.

doi:10.1007/s10858-006-9047-4

Cited by 19 publications

(30 citation statements)

References 49 publications

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“…2 B and D). The three vectors are reporting on different motions, consistent with a study by Wang et al (38), and none fully reflects the BB entropy (Fig. 2C and Fig.…”

Section: Discussionsupporting

confidence: 90%

“…Because the calculations are based on the same data, they should agree if they report on the same quantity (38). Given that they produce disparate values, we conclude that the three vectors are reporting on different motions (38) and are not true proxies of the total BB entropy. Nevertheless, a single model relating each vector's S LZ 2 value to its own entropy, rather than the BB entropy, successfully describes both helical and sheet residues (32) (Fig.…”

Section: Resultsmentioning

confidence: 89%

See 1 more Smart Citation

Loss of conformational entropy in protein folding calculated using realistic ensembles and its implications for NMR-based calculations

Baxa¹,

Haddadian²,

Jumper³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

113

104

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The loss of conformational entropy is a major contribution in the thermodynamics of protein folding. However, accurate determination of the quantity has proven challenging. We calculate this loss using molecular dynamic simulations of both the native protein and a realistic denatured state ensemble. For ubiquitin, the total change in entropy is TΔS Total = 1.4 kcal·mol −1 per residue at 300 K with only 20% from the loss of side-chain entropy. Our analysis exhibits mixed agreement with prior studies because of the use of more accurate ensembles and contributions from correlated motions. Buried side chains lose only a factor of 1.4 in the number of conformations available per rotamer upon folding (Ω U /Ω N ). The entropy loss for helical and sheet residues differs due to the smaller motions of helical residues (TΔS helix−sheet = 0.5 kcal·mol NMR order parameters | molecular dynamics | helix propensity | sheet propensity | denatured state A n accurate determination of the loss of conformational entropy is critical for dissecting the energetics of reactions involving protein motions, including folding, conformational change, and binding (1-6). Given the difficulty of directly measuring the conformational entropy, most early estimates relied on computational approaches (2, 7-10), although, more recently, NMR methods have been used to measure site-resolved entropies (11). The computational methods often calculated the entropy of either the native state ensemble (NSE) or the denatured state ensemble (DSE) and invoked assumptions about the entropy of the other ensemble [e.g., assuming the NSE is a single state or that the DSE is a composite of all side-chain (SC) rotameric states in the Protein Data Bank (PDB)]. Most previous approaches focused on helices and omitted contributions from vibrations and correlated motions (12, 13), thereby partly accounting for the spectrum of calculated values.We address these issues by calculating the chain's conformational entropy from the distributions of the backbone (BB) (ϕ,ψ) and SC rotametric angles, [χ n ], obtained from all-atom simulations of the NSE and DSE for mammalian ubiquitin (Ub). This study extends our previous calculation of the loss of BB entropy that used an experimentally validated DSE (14). The calculated angular distributions reflect both the Ramachandran (Rama) basin populations and the torsional vibrations. Correlated motions are accounted for through the use of joint probability distributions [e.g., P(ϕ,ψ,χ 1 ,χ 2 )].The computed loss of BB entropy is 80% of the total entropy loss at 300 K. The BB entropy is independent of burial and residue type (excluding Pro, Gly, and pre-Pro residues) but depends on the secondary structure. Helical residues lose more BB entropy than sheet residues, TΔS helix−sheet = 0.5 kcal·mol −1 at 300 K, a difference not fully reflected by either amide N-H or carbonyl C=O bond NMR order parameters. The SC entropy loss, TΔS SC ∼ 0.2 kcal·mol −1 ·rotamer −1 , is largely independent of 2°structure and weakly correlated with burial. Combinin...

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“…2 B and D). The three vectors are reporting on different motions, consistent with a study by Wang et al (38), and none fully reflects the BB entropy (Fig. 2C and Fig.…”

Section: Discussionsupporting

confidence: 90%

Section: Resultsmentioning

confidence: 89%

Loss of conformational entropy in protein folding calculated using realistic ensembles and its implications for NMR-based calculations

Baxa¹,

Haddadian²,

Jumper³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

113

104

View full text Add to dashboard Cite

show abstract

“…Other less commonly used nuclei are 13 C′ and/or 13 C α . (Chang and Tjandra 2005;Pang et al 2002;Wang et al 2005;Wang et al 2006;Zeng et al 1996) However the accurate measurement and interpretation of 13 C relaxation is more complicated. A less commonly known approach uses the interference effects of cross-correlated relaxation mechanisms, which have been utilized to great advantage in TROSY (Pervushin et al 1997;Riek et al 1999;Salzmann et al 1998) and Methyl-TROSY methodology (Tugarinov et al 2003;Kay 2004a, 2004b;Tugarinov et al 2004) for the study of large molecular weight systems.…”

Section: Cross-correlated Relaxation (Ccr) To Define Backbone Conformmentioning

confidence: 99%

NMR Spectroscopic Studies of the Conformational Ensembles of Intrinsically Disordered Proteins

Kurzbach

Kontaxis

Coudevylle

et al. 2015

Advances in Experimental Medicine and Biology

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Intrinsically disordered proteins (IDPs) are characterized by substantial conformational flexibility and thus not amenable to conventional structural biology techniques. Given their inherent structural flexibility NMR spectroscopy offers unique opportunities for structural and dynamic studies of IDPs. The past two decades have witnessed significant development of NMR spectroscopy that couples advances in spin physics and chemistry with a broad range of applications. This chapter will summarize key advances in NMR methodology. Despite the availability of efficient (multi-dimensional) NMR experiments for signal assignment of IDPs it is discussed that NMR of larger and more complex IDPs demands spectral simplification strategies capitalizing on specific isotope-labeling strategies. Prototypical applications of isotope labeling-strategies are described. Since IDP-ligand association and dissociation processes frequently occur on time scales that are amenable to NMR spectroscopy we describe in detail the application of CPMG relaxation dispersion techniques to studies of IDP protein binding. Finally, we demonstrate that the complementary usage of NMR and EPR data provide a more comprehensive picture about the conformational states of IDPs and can be employed to analyze the conformational ensembles of IDPs.

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“…The most common experiments measure relaxation rate constants of 15 N [1,2] and carbonyl 13 C [3][4][5][6] nuclei for the protein backbone, as well as methyl 13 C and deuterium ( 2 D) [7][8][9][10] nuclei for sidechains. All of these experiments detect the final signal via proton ( 1 H) nuclei.…”

Section: Introductionmentioning

confidence: 99%

Direct 13C-detection for carbonyl relaxation studies of protein dynamics

Pasat

Zintsmaster

Peng

2008

Journal of Magnetic Resonance

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Quantifying Lipari–Szabo modelfree parameters from 13CO NMR relaxation experiments

Cited by 19 publications

References 49 publications

Loss of conformational entropy in protein folding calculated using realistic ensembles and its implications for NMR-based calculations

Loss of conformational entropy in protein folding calculated using realistic ensembles and its implications for NMR-based calculations

NMR Spectroscopic Studies of the Conformational Ensembles of Intrinsically Disordered Proteins

Direct 13C-detection for carbonyl relaxation studies of protein dynamics

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