Browse
Submit Data
Databases
API
Help

Dataset Information

24 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Deep UV resonance Raman spectroscopy of ?-sheet amyloid fibrils: a QM/MM simulation.

ABSTRACT: We present a combined quantum mechanics and molecular mechanics study of the deep ultraviolet ??* resonance Raman spectra of ?-sheet amyloid fibrils A?(34-42) and A?(1-40). Effects of conformational fluctuations are described using a Ramachandran angle map, thus avoiding repeated ab initio calculations. Experimentally observed effects of hydrogen-deuterium exchange are reproduced. We propose that the AmIII band redshift upon deuteration is caused by the loss of coupling between C(?)-H bending and N-D bending modes, rather than by peptide bond hydration.

SUBMITTER: Ren H

PROVIDER: S-EPMC3233492 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Deep UV resonance Raman spectroscopy of β-sheet amyloid fibrils: a QM/MM simulation.

Ren Hao H Jiang Jun J Mukamel Shaul S

The journal of physical chemistry. B 20111107 47

We present a combined quantum mechanics and molecular mechanics study of the deep ultraviolet ππ* resonance Raman spectra of β-sheet amyloid fibrils Aβ(34-42) and Aβ(1-40). Effects of conformational fluctuations are described using a Ramachandran angle map, thus avoiding repeated ab initio calculations. Experimentally observed effects of hydrogen-deuterium exchange are reproduced. We propose that the AmIII band redshift upon deuteration is caused by the loss of coupling between C(α)-H bending an ...[more]

PMID: 22007849

Similar Datasets

Structural features of ?-synuclein amyloid fibrils revealed by Raman spectroscopy.

Project description:Parkinson's disease (PD) is associated with the formation of ?-synuclein amyloid fibrils. Elucidating the role of these ?-sheet-rich fibrils in disease progression is crucial; however, collecting detailed structural information on amyloids is inherently difficult because of their insoluble, non-crystalline, and polymorphic nature. Here, we show that Raman spectroscopy is a facile technique for characterizing structural features of ?-synuclein fibrils. Combining Raman spectroscopy with aggregation kinetics and transmission electron microscopy, we examined the effects of pH and ionic strength as well as four PD-related mutations (A30P, E46K, G51D, and A53T) on ?-synuclein fibrils. Raman spectral differences were observed in the amide-I, amide-III, and fingerprint regions, indicating that secondary structure and tertiary contacts are influenced by pH and to a lesser extent by NaCl. Faster aggregation times appear to facilitate unique fibril structure as determined by the highly reproducible amide-I band widths, linking aggregation propensity and fibril polymorphism. Importantly, Raman spectroscopy revealed molecular-level perturbations of fibril conformation by the PD-related mutations that are not apparent through transmission electron microscopy or limited proteolysis. The amide-III band was found to be particularly sensitive, with G51D exhibiting the most distinctive features, followed by A53T and E46K. Relating to a cellular environment, our data would suggest that fibril polymorphs can be formed in different cellular compartments and potentially result in distinct phenotypes. Our work sets a foundation toward future cellular Raman studies of amyloids.

| S-EPMC5777252 | biostudies-literature

Simulation of two-dimensional ultraviolet spectroscopy of amyloid fibrils.

Project description:Revealing the structure and aggregation mechanism of amyloid fibrils is essential for the treatment of over 20 diseases related to protein misfolding. Coherent two-dimensional (2D) infrared spectroscopy is a novel tool that provides a wealth of new insight into the structure and dynamics of biomolecular systems. Recently developed ultrafast laser sources are extending multidimensional spectroscopy into the ultraviolet (UV) region, and this opens up new opportunities for probing fibrils. In a simulation study, we show that 2DUV spectra of the backbone of a 32-residue ?-amyloid (A?(9-40)) fibril associated with Alzheimer's disease and two intermediate prefibrillar structures carry characteristic signatures of fibril size and geometry that could be used to monitor its formation kinetics. The dependence of these signals on the fibril size and geometry is explored. We demonstrate that the dominant features of the ?-amyloid fibril spectra are determined by intramolecular interactions within a single A?(9-40), and intermolecular interactions at the "external interface" have clear signatures in the fine details of these signals.

| S-EPMC2953465 | biostudies-literature

Dissecting structure of prion amyloid fibrils by hydrogen-deuterium exchange ultraviolet Raman spectroscopy.

Project description:The molecular mechanisms underlying structural diversity of amyloid fibrils or prion strains formed within the same primary structure is considered to be one of the most enigmatic questions in prion biology. We report here on the direct characterization of amyloid structures using a novel spectroscopic technique, hydrogen-deuterium exchange ultraviolet Raman spectroscopy. This method enables us to assess the structural differences within highly ordered cross-?-cores of two amyloid states produced within the same amino acid sequence of full-length mammalian prion protein. We found that while both amyloid states consisted of ?-structures, their cross-?-cores exhibited hydrogen bonding of different strengths. Moreover, Raman spectroscopy revealed that both amyloid states displayed equally narrow crystalline-like bands, suggesting uniform structures of cross-?-cores within each state. Taken together, these data suggest that highly polymorphous fibrils can display highly uniform structures of their cross-?-core and belong to the same prion strain.

| S-EPMC3490051 | biostudies-literature

QM/MM Simulation on P450 BM3 Enzyme Catalysis Mechanism.

Project description:Using a structure generated by induced fit modeling of the protein-ligand complex, the reaction path for hydrogen atom abstraction in P450 BM3 is studied by means of mixed QM/MM methods to determine the structures and energetics along the reaction path. The IFD structure is suitable for hydrogen atom abstraction at the ?-1 position. The electronic structures obtained are similar to those observed in P450 cam. We show that the barrier for the hydrogen abstraction step from QM/MM modeling is 13.3 kcal/mol in quartet and 15.6 kcal/mol in doublet. Although there is some strain energy present in the ligand, the activation barrier is not dramatically affected. A crystal water molecule, HOH502, plays a role as catalyst and decreases the activation barrier by about 2 kcal/mol and reaction energy by about 3-4 kcal/mol. In order to achieve reactive chemistry at the remaining experimentally observed positions in the hydrocarbon tail of the ligand, other structures would have to be utilized as a starting point for the reaction. Finally, the present results still leave open the question of whether DFT methods provide an accurate computation of the barrier height in the P450 hydrogen atom abstraction reaction.

| S-EPMC2757081 | biostudies-literature

Real-Time Monitoring of Enzyme-Catalysed Reactions using Deep UV Resonance Raman Spectroscopy.

Project description:For enzyme-catalysed biotransformations, continuous in situ detection methods minimise the need for sample manipulation, ultimately leading to more accurate real-time kinetic determinations of substrate(s) and product(s). We have established for the first time an on-line, real-time quantitative approach to monitor simultaneously multiple biotransformations based on UV resonance Raman (UVRR) spectroscopy. To exemplify the generality and versatility of this approach, multiple substrates and enzyme systems were used involving nitrile hydratase (NHase) and xanthine oxidase (XO), both of which are of industrial and biological significance, and incorporate multistep enzymatic conversions. Multivariate data analysis of the UVRR spectra, involving multivariate curve resolution-alternating least squares (MCR-ALS), was employed to effect absolute quantification of substrate(s) and product(s); repeated benchmarking of UVRR combined with MCR-ALS by HPLC confirmed excellent reproducibility.

| S-EPMC5488198 | biostudies-literature

Structural Studies of Amyloid Fibrils by Paramagnetic Solid-State Nuclear Magnetic Resonance Spectroscopy.

Project description:Application of paramagnetic solid-state NMR to amyloids is demonstrated, using Y145Stop human prion protein modified with nitroxide spin-label or EDTA-Cu2+ tags as a model. By using sample preparation protocols based on seeding with preformed fibrils, we show that paramagnetic protein analogs can be induced into adopting the wild-type amyloid structure. Measurements of residue-specific intramolecular and intermolecular paramagnetic relaxation enhancements enable determination of protein fold within the fibril core and protofilament assembly. These methods are expected to be widely applicable to other amyloids and protein assemblies.

| S-EPMC6193843 | biostudies-literature

A QM/MM Derived Polarizable Water Model for Molecular Simulation.

Project description:In this work, we propose an improved QM/MM-based strategy to determine condensed-phase polarizabilities and we use this approach to optimize a new and simple polarizable four-site water model for classical molecular simulation. For the determination of the model value for the polarizability from QM/MM, we show that our proposed consensus-fitting strategy significantly reduces the uncertainty in calculated polarizabilities in cases where the size of the local external electric field is small. By fitting electrostatic, polarization and dispersion properties of our water model based on quantum and/or combined QM/MM calculations, only a single model parameter (describing exchange repulsion) is left for empirical calibration. The resulting model performs well in describing relevant pure-liquid thermodynamic and transport properties, which illustrates the merit of our approach to minimize the number of free variables in our model.

| S-EPMC6321318 | biostudies-literature

UV resonance Raman spectroscopy monitors polyglutamine backbone and side chain hydrogen bonding and fibrillization.

Project description:We utilize 198 and 204 nm excited UV resonance Raman spectroscopy (UVRR) and circular dichroism spectroscopy (CD) to monitor the backbone conformation and the Gln side chain hydrogen bonding (HB) of a short, mainly polyGln peptide with a D(2)Q(10)K(2) sequence (Q10). We measured the UVRR spectra of valeramide to determine the dependence of the primary amide vibrations on amide HB. We observe that a nondisaggregated Q10 (NDQ10) solution (prepared by directly dissolving the original synthesized peptide in pure water) exists in a ?-sheet conformation, where the Gln side chains form hydrogen bonds to either the backbone or other Gln side chains. At 60 °C, these solutions readily form amyloid fibrils. We used the polyGln disaggregation protocol of Wetzel et al. [Wetzel, R., et al. (2006) Methods Enzymol.413, 34-74] to dissolve the Q10 ?-sheet aggregates. We observe that the disaggregated Q10 (DQ10) solutions adopt PPII-like and 2.5(1)-helix conformations where the Gln side chains form hydrogen bonds with water. In contrast, these samples do not form fibrils. The NDQ10 ?-sheet solution structure is essentially identical to that found in the NDQ10 solid formed upon evaporation of the solution. The DQ10 PPII and 2.5(1)-helix solution structure is essentially identical to that in the DQ10 solid. Although the NDQ10 solution readily forms fibrils when heated, the DQ10 solution does not form fibrils unless seeded with the NDQ10 solution. This result demonstrates very high activation barriers between these solution conformations. The NDQ10 fibril secondary structure is essentially identical to that of the NDQ10 solution, except that the NDQ10 fibril backbone conformational distribution is narrower than in the dissolved species. The NDQ10 fibril Gln side chain geometry is more constrained than when NDQ10 is in solution. The NDQ10 fibril structure is identical to that of the DQ10 fibril seeded by the NDQ10 solution.

| S-EPMC3415266 | biostudies-literature

UV Resonance Raman Spectroscopy as a Tool to Probe Membrane Protein Structure and Dynamics.

Project description:Ultraviolet resonance Raman (UVRR) spectroscopy is a vibrational technique that reveals structures and dynamics of biological macromolecules without the use of extrinsic labels. By tuning the Raman excitation wavelength to the deep UV region (e.g., 228 nm), Raman signal from tryptophan and tyrosine residues are selectively enhanced, allowing for the study of these functionally relevant amino acids in lipid and aqueous environments. In this chapter, we present methods on the UVRR data acquisition and analysis of the tryptophan vibrational modes of a model β-barrel membrane protein, OmpA, in folded and unfolded conformations.

| S-EPMC6874512 | biostudies-literature

Surface-sensitive Raman spectroscopy of collagen I fibrils.

Project description:Collagen fibrils are the main constituent of the extracellular matrix surrounding eukaryotic cells. Although the assembly and structure of collagen fibrils is well characterized, very little appears to be known about one of the key determinants of their biological function-namely, the physico-chemical properties of their surface. One way to obtain surface-sensitive structural and chemical data is to take advantage of the near-field nature of surface- and tip-enhanced Raman spectroscopy. Using Ag and Au nanoparticles bound to Collagen type-I fibrils, as well as tips coated with a thin layer of Ag, we obtained Raman spectra characteristic to the first layer of collagen molecules at the surface of the fibrils. The most frequent Raman peaks were attributed to aromatic residues such as phenylalanine and tyrosine. In several instances, we also observed Amide I bands with a full width at half-maximum of 10-30 cm(-1). The assignment of these Amide I band positions suggests the presence of 3(10)-helices as well as ?- and ?-sheets at the fibril's surface.

| S-EPMC3072603 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data