Dataset Information

Study of the ?D-crystallin protein using two-dimensional infrared (2DIR) spectroscopy: experiment and simulation.

ABSTRACT: Cataracts is a misfolding protein disease in which one of the major components is the ?D-crystallin protein. The conformational structure of the aggregated ?D-crystallin and the interactions that cause aggregation are largely unknown. A recent experimental two-dimensional infrared (2DIR) spectroscopy study determined that the C-terminal domain has a high propensity to form ?-sheets whereas the N-terminal domain forms a disordered structure in the fiber state. We present a combined computational molecular dynamics and infrared spectroscopy study of the local dynamics of these domains. The computed 2DIR signals agree remarkably well with experiment. We show that the two domains, both of which have a Greek key structural fold, experience different electrostatic environments, which may be related to the fact that the C-terminal domain is more structurally stable than the N-terminal domain. We correlate the vibrational couplings to known energy dissipation mechanisms and reveal their origin.

SUBMITTER: Lam AR

PROVIDER: S-EPMC3865159 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Study of the γD-crystallin protein using two-dimensional infrared (2DIR) spectroscopy: experiment and simulation.

Lam A R AR Moran S D SD Preketes N K NK Zhang T O TO Zanni M T MT Mukamel S S

The journal of physical chemistry. B 20130918 49

Cataracts is a misfolding protein disease in which one of the major components is the γD-crystallin protein. The conformational structure of the aggregated γD-crystallin and the interactions that cause aggregation are largely unknown. A recent experimental two-dimensional infrared (2DIR) spectroscopy study determined that the C-terminal domain has a high propensity to form β-sheets whereas the N-terminal domain forms a disordered structure in the fiber state. We present a combined computational ...[more]

PMID: 23972032

Similar Datasets

Project description:We have studied the structure of (Ala)5, a model unfolded peptide, using a combination of 2D IR spectroscopy and molecular dynamics (MD) simulation. Two different isotopomers, each bis-labeled with (13)C?O and (13)C?(18)O, were strategically designed to shift individual site frequencies and uncouple neighboring amide-I' modes. 2D IR spectra taken under the double-crossed ??/4, -?/4, Y, Z? polarization show that the labeled four-oscillator systems can be approximated by three two-oscillator systems. By utilizing the different polarization dependence of diagonal and cross peaks, we extracted the coupling constants and angles between three pairs of amide-I' transition dipoles through spectral fitting. These parameters were related to the peptide backbone dihedral angles through DFT calculated maps. The derived dihedral angles are all located in the polyproline-II (ppII) region of the Ramachandran plot. These results were compared to the conformations sampled by Hamiltonian replica-exchange MD simulations with three different CHARMM force fields. The C36 force field predicted that ppII is the dominant conformation, consistent with the experimental findings, whereas C22/CMAP predicted similar population for ?+, ?, and ppII, and the polarizable Drude-2013 predicted dominating ? structure. Spectral simulation based on MD representative conformations and structure ensembles demonstrated the need to include multiple 2D spectral features, especially the cross-peak intensity ratio and shape, in structure determination. Using 2D reference spectra defined by the C36 structure ensemble, the best spectral simulation is achieved with nearly 100% ppII population, although the agreement with the experimental cross-peak intensity ratio is still insufficient. The dependence of population determination on the choice of reference structures/spectra and the current limitations on theoretical modeling relating peptide structures to spectral parameters are discussed. Compared with the previous results on alanine based oligopeptides, the dihedral angles of our fitted structure, and the most populated ppII structure from the C36 simulation are in good agreement with those suggesting a major ppII population. Our results provide further support for the importance of ppII conformation in the ensemble of unfolded peptides.

Dataset Information

Study of the ?D-crystallin protein using two-dimensional infrared (2DIR) spectroscopy: experiment and simulation.

Publications

Study of the γD-crystallin protein using two-dimensional infrared (2DIR) spectroscopy: experiment and simulation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets