Protein Apparent Dielectric Constant and Its Temperature Dependence from Remote Chemical Shift Effects

An, Liaoyuan; Wang, Yefei; Zhang, Ning; Yan, Shihai; Bax, Ad; Yao, Lishan

doi:10.1021/ja505852b

Cited by 14 publications

(20 citation statements)

References 39 publications

(70 reference statements)

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“…To test this, the PCM model was employed around both the 5 Å and larger 7–8 Å clusters to capture bulk contributions equivalently. Much discussion surrounds the appropriate dielectric constant to use (Schutz and Warshel (2001); Li et al (2013); Kukic et al (2013); An et al (2014)), but values around 4 are common. Here, we consider three different dielectric constants: ε = 2, 4, or 8.…”

Section: Resultsmentioning

confidence: 99%

Converging nuclear magnetic shielding calculations with respect to basis and system size in protein systems

et al. 2015

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Ab initio chemical shielding calculations greatly facilitate the interpretation of nuclear magnetic resonance (NMR) chemical shifts in biological systems, but the large sizes of these systems requires approximations in the chemical models used to represent them. Achieving good convergence in the predicted chemical shieldings is necessary before one can unravel how other complex structural and dynamical factors affect the NMR measurements. Here, we investigate how to balance trade-offs between using a better basis set or a larger cluster model for predicting the chemical shieldings of the substrates in two representative examples of protein-substrate systems involving different domains in tryptophan synthase: the N-(4′-trifluoromethoxybenzoyl)-2-aminoethyl phosphate (F9) ligand which binds in the α active site, and the 2-aminophenol (2AP) quinonoid intermediate formed in the β active site. We first demonstrate that a chemically intuitive three-layer, locally dense basis model that uses a large basis on the substrate, a medium triple-zeta basis to describe its hydrogen-bonding partners and/or surrounding van derWaals cavity, and a crude basis set for more distant atoms provides chemical shieldings in good agreement with much more expensive large basis calculations. Second, long-range quantum mechanical interactions are important, and one can accurately estimate them as a small-basis correction to larger-basis calculations on a smaller cluster. The combination of these approaches enables one to perform density functional theory NMR chemical shift calculations in protein systems that are well-converged with respect to both basis set and cluster size.

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Section: Resultsmentioning

confidence: 99%

Converging nuclear magnetic shielding calculations with respect to basis and system size in protein systems

et al. 2015

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“…In this work, the K31H mutant was 15 N/ 13 C‐labeled whereas the K31H, E27Q mutant was 15 N‐labeled only. The two protein samples were mixed together in a 2 m m NaCl solution and titrated with HCl or NaOH to change the pH values, and the 1 H‐ 15 N spectra were recorded at 283, 290.5, 298, 305.5, and 313 K with an interleaved pulse sequence to separate the signals from the two proteins (Figures A and Figure S2) . Because there are no other histidine residues in GB3, the backbone 1 H‐ 15 N spectra can be used for p K a fitting of the mutated histidine residue.…”

Section: Figurementioning

confidence: 99%

“… pH titration of the mixed K31H ( 15 N/ 13 C‐labeled, red) and K31H, E27Q ( 15 N‐labeled, black) sample. A) The 1 H‐ 15 N signals (H31 at 298 K, pH 5.1) of the mixed proteins were separated by an interleaved experiment using a 13 C filter (Figure S2) . The 15 N chemical shift of H31 at different pH values was fitted to the Henderson–Hasselbalch equation to yield p K a values at 283 K (B), 290.5 K (C), 298 K (D), 305.5 K (E), and 313 K (F).…”

Section: Figurementioning

confidence: 99%

Entropy Drives the Formation of Salt Bridges in the Protein GB3

Zhang

Wang

et al. 2017

Angew Chem Int Ed

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Salt bridges are very common in proteins.But what drives the formation of protein salt bridges is not clear.Inthis work, we determined the strength of four salt bridges in the protein GB3 by measuring the DpK a values of the basic residues that constitute the salt bridges with ah ighly accurate NMR titration method at different temperatures.T he results show that the DpK a values increase with temperature,t hus indicating that the salt bridges are stronger at higher temperatures.Fitting of DpK a values to the vantHoff equation yields positive DHand DSvalues,thus indicating that entropydrives salt-bridge formation. Molecular dynamics simulations show that the protein and solvent make opposite contributions to DH and DS. Specifically,t he enthalpic gain contributed from the protein is more than offset by the enthalpic loss contributed from the solvent, whereas the entropic gain originates from the desolvation effect.

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“…pK a values can be determined through pH titrations.Inthis work, the K31H mutant was 15 N/ 13 C-labeled whereas the K31H, E27Q mutant was 15 N-labeled only.The two protein samples were mixed together in a2mm NaCl solution and titrated with HCl or NaOH to change the pH values,and the 1 H- 15 Nspectra were recorded at 283, 290.5, 298, 305.5, and 313 Kw ith an interleaved pulse sequence to separate the signals from the two proteins (Figures 1A and Figure S2). [12] Because there are no other histidine residues in GB3, the backbone 1 H- 15 Nspectra can be used for pK a fitting of the mutated histidine residue.T hese spectra have am uch higher signal-to-noise ratio than the side-chain spectra usually recorded for pK a fitting.Since the two proteins were dissolved in the same solution, the main DpK a uncertainty originated from the pH measurement error was eliminated. Theidentical environment experienced by the two proteins also minimized effects caused by variation in ionic strength and temperature in otherwise separate samples.…”

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confidence: 99%

“…DG solv and DG prot also show opposite behavior, that is, DG solv decreases but DG prot increases with temperature.T he total DG decreases with temperature but with amuch shallower slope than that of Ns ignals (H31 at 298 K, pH 5.1) of the mixed proteins were separated by an interleaved experimentusing a 13 Cfilter ( Figure S2). [12] The Table 1. A) The total free energy DG (black square), the solvent contribution DG solv (red dot), and the protein contribution DG prot (blue triangle) are plotted against temperature.…”

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confidence: 99%