Recent results on hydrogen and hydration in biology studied by neutron macromolecular crystallography

Nakabayashi, Nobuo; Arai, Shigeki; Kurihara, Kazuo; Chatake, Toshiyuki; Tanaka, Ichiro; Bau, Robert

doi:10.1007/s00018-005-5418-3

Cited by 49 publications

(35 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The interpretation of protein dynamics from crystal structures is traditionally limited to direct observation of conformational differences in independent molecules within the same asymmetric unit 8 or independent crystal structures. 9,10 In addition, proteins in crystals exchange hydrogens with solvent, 11 undergo reversible conformational changes, 12 and catalyze chemical reactions as complex as DNA polymerization. 13 These and many other examples indicate that many proteins in crystals can undergo small-and large-scale motions and populate diverse conformations.…”

Section: Introductionmentioning

confidence: 99%

Automated electron‐density sampling reveals widespread conformational polymorphism in proteins

et al. 2010

View full text Add to dashboard Cite

Although proteins populate large structural ensembles, X-ray diffraction data are traditionally interpreted using a single model. To search for evidence of alternate conformers, we developed a program, Ringer, which systematically samples electron density around the dihedral angles of protein side chains. In a diverse set of 402 structures, Ringer identified weak, nonrandom electron-density features that suggest of the presence of hidden, lowly populated conformations for >18% of uniquely modeled residues. Although these peaks occur at electron-density levels traditionally regarded as noise, statistically significant (P < 10 25 ) enrichment of peaks at successive rotameric v angles validates the assignment of these features as unmodeled conformations. Weak electron density corresponding to alternate rotamers also was detected in an accurate electron density map free of model bias. Ringer analysis of the high-resolution structures of free and peptide-bound calmodulin identified shifts in ensembles and connected the alternate conformations to ligand recognition. These results show that the signal in high-resolution electron density maps extends below the traditional 1 r cutoff, and crystalline proteins are more polymorphic than current crystallographic models. Ringer provides an objective, systematic method to identify previously undiscovered alternate conformations that can mediate protein folding and function.

show abstract

Section: Introductionmentioning

confidence: 99%

Automated electron‐density sampling reveals widespread conformational polymorphism in proteins

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Advances in experimental probes such as neutron scattering [52], nuclear magnetic resonance (NMR) [8], femtosecond laser spectroscopy, [53] and dielectric dispersion [54] has allowed a quantitative description of the properties of the water molecules associated with specific parts of the solvated protein. Key quantities that can be determined include, (a) the occupancy (i.e., the probability that a water molecule will be found at the site), (b) the residence time (the timescale for exchange of the water molecule with the surrounding bulk water), and (c) the "order parameter" which is a measure of the rotational freedom of the water molecule at the site.…”

Section: Introductionmentioning

confidence: 99%

Quantum Dynamics of Electronic Excitations in Biomolecular Chromophores: Role of the Protein Environment and Solvent

2008

View full text Add to dashboard Cite

We consider continuum dielectric models as minimal models to understand the effect of a surrounding globular protein and solvent on the quantum dynamics of electronic excitations in a biological chromophore. For these models we derive expressions for the frequency dependent spectral density which describes the coupling of the electronic levels in the chromophore to its environment. The magnitude and frequency dependence of the spectral density determines whether or not the quantum dynamics is coherent or incoherent, and thus whether on not one can observe quantum interference effects such as Rabi oscillations. We find the contributions to the spectral density from each component of the chromophore environment: the bulk solvent, protein, and water bound to the protein. The relative importance of each component to the quantum dynamics of the chromophore is determined by the time scale on which one is considering the dynamics. Our results provide a natural explanation and model for the different time scales observed in the spectral density extracted from the solvation dynamics probed by ultra-fast laser spectroscopy techniques such as the dynamic Stokes shift and three pulse photon echo spectroscopy. Our results are used to define under what conditions the dynamics of the excited chromophore is dominated by the surrounding protein and when it is dominated by dielectric fluctuations in the solvent. We show that even when the chromophore is shielded from the solvent by the protein ultra-fast solvation can be dominated by the solvent. Hence, we suggest that the ultra-fast solvation recently seen in some biological chromophores should not necessarily be assigned to ultra-fast protein dynamics. The magnitudes of the spectral density that we estimate from our continuum models and extracted from experiment suggest that most quantum dynamics of electronic excitations is incoherent. A possible exception is transfer of excitons between neigbouring chromophores in photosynthetic systems.

show abstract

“…The atomic coordinates for glycine (GLYCIN20), alanine (LALNIN12), glycine hydrochloride (GLYHCL), valine hydrochloride (VALEHC11), glutamic acid hydrochloride (LGLUTA), phenylalanine hydrochloride (PHALNC01), tyrosine hydrochloride (LTYRHC10), cytosine (CYTSIN01), and thymine (THYMIN01) were derived from the Cambridge Crystallographic Database. 27 Where available, neutron diffraction structures were used, since even hydrogen atoms are 4 accurately located by neutron diffraction 28 (in contrast to X-ray diffraction). The neutron diffraction structures were used without optimization of the atomic coordinates for calculations of static NMR parameters.…”

mentioning

confidence: 99%

A molecular dynamics study of the effects of fast molecular motions on solid-state NMR parameters

Dračínský

Hodgkinson

2013

CrystEngComm

View full text Add to dashboard Cite

Citation for published item:hr § ¡ %nsk¡ yD wrtin nd rodgkinsonD ul @PHIQA 9e moleulr dynmis study of the e'ets of fst moleulr motions on solidEstte xw prmetersF9D grystinggommFD IS @RQAF ppF VUHSEVUIPF Further information on publisher's website: httpXGGdxFdoiForgGIHFIHQWGQeRHTIP Publisher's copyright statement:Additional information: Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. AbstractThe influence of fast molecular motions on NMR parameters in molecular organic solids is explored on a set of amino acids and nucleic acid bases. A combination of DFT molecular dynamics and calculations of shielding and electric field gradient (EFG) tensors reveals the impact of vibrational motions on isotropic chemical shifts, chemical shift anisotropies (CSAs) and quadrupolar interactions. We demonstrate that molecular motion has a significant effect on average molecular structures, and that neglecting the effects of motion on crystal structures derived by diffraction methods may lead to significant errors of calculated isotropic chemical shifts. Re-orientation of the NMR tensors by molecular motion reduces the magnitudes of the NMR anisotropies, and inclusion of molecular dynamics can significantly improve the agreement between calculated quadrupolar couplings and experimental values.

show abstract

Recent results on hydrogen and hydration in biology studied by neutron macromolecular crystallography

Cited by 49 publications

References 69 publications

Automated electron‐density sampling reveals widespread conformational polymorphism in proteins

Automated electron‐density sampling reveals widespread conformational polymorphism in proteins

Quantum Dynamics of Electronic Excitations in Biomolecular Chromophores: Role of the Protein Environment and Solvent

A molecular dynamics study of the effects of fast molecular motions on solid-state NMR parameters

Contact Info

Product

Resources

About