Yaroslav Ryabov

Non-Debye dielectric relaxation in complex materials

Abstract The paper considers several examples of non-Debye dielectric response in complex heterogeneous media. The percolation phenomenon and Cole–Cole relaxation in disordered matter are discussed in detail. The proposed models are illustrated by different sample systems: ionic microemulsions, porous glasses, porous silicon, polymer–water mixtures, and polymer–microcomposite materials. The models enable us to establish the relationship between the parameters of dielectric relaxation broadening, structural properties of the media and transport features of charge carriers in the considered systems. In addition, the origins of “strange kinetic” phenomena were discussed based on statistical physics and fractional time evolution ideas.

Interdomain mobility in di-ubiquitin revealed by NMR

Domain orientation and dynamics can play an essential role in the function of multidomain proteins. Lys48‐linked polyubiquitin chains, the principal signal for proteasomal protein degradation, adopt a closed conformation at physiological conditions, in which the functionally important residues Leu8, Ile44, and Val70 are sequestered at the interdomain interface. This interface must open in order for these groups to become available for interactions with various chain‐recognition factors. Knowledge of the mechanism of domain motion leading to the opening of the interdomain interface in polyubiqutin is, therefore, essential for the understanding of the processes controlling molecular recognition events in polyubiquitin signaling. Here we use NMR to characterize the interdomain dynamics that open the interface in a di‐ubiquitin chain. This process occurs via domain reorientations on a 10‐ns time scale and with the amplitudes that are sufficient for making functionally important hydrophobic residues in polyubiquitin available for direct interactions with various ubiquitin‐binding factors. The analysis revealed the structures of the interconverting conformational states of di‐ubiquitin and the rates and amplitudes of this process at near‐physiological and acidic pH. The proposed mechanism of domain reorientation is quite general and could serve as a paradigm of interdomain mobility in other multidomain systems. Proteins 2006.

The symmetric broadening of the water relaxation peak in polymer–water mixtures and its relationship to the hydrophilic and hydrophobic properties of polymers

The dielectric relaxation of water molecules in polymer–water mixtures is discussed. The memory function approach and scaling relationships are used as a basis for the model of symmetric dielectric spectrum broadening. The correspondence between the relaxation time, the geometrical properties, the self-diffusion coefficient, and the Cole–Cole exponent is established. The relationship between the hydrophilic and hydrophobic properties of the polymers and the dielectric relaxation parameters is discussed.

Using the Experimentally Determined Components of the Overall Rotational Diffusion Tensor to Restrain Molecular Shape and Size in NMR Structure Determination of Globular Proteins and Protein-Protein Complexes

This paper describes an approach for making use of the components of the experimentally determined rotational diffusion tensor derived from NMR relaxation measurements in macromolecular structure determination. The parameters of the rotational diffusion tensor describe the shape and size of the macromolecule or macromolecular complex, and are therefore complementary to traditional NMR restraints. The structural information contained in the rotational diffusion tensor is not dissimilar to that present in the small-angle region of solution X-ray scattering profiles. We demonstrate the utility of rotational diffusion tensor restraints for protein structure refinement using the N-terminal domain of enzyme I (EIN) as an example and validate the results by solution small-angle X-ray scattering. We also show how rotational diffusion tensor restraints can be used for docking complexes using the dimeric HIV-1 protease and the EIN-HPr complexes as examples. In the former case, the rotational diffusion tensor restraints are sufficient in their own right to determine the position of one subunit relative to another. In the latter case, rotational diffusion tensor restraints complemented by highly ambiguous distance restraints derived from chemical shift perturbation mapping and a hydrophobic contact potential are sufficient to correctly dock EIN to HPr. In each case, the cluster containing the lowest-energy structure corresponds to the correct solution.

Direct Use of 15N Relaxation Rates as Experimental Restraints on Molecular Shape and Orientation for Docking of Protein−Protein Complexes

(15)N relaxation rates contain information on overall molecular shape and size, as well as residue specific orientations of N-H bond vectors relative to the axes of the diffusion tensor. Here we describe a pseudopotential E(relax) that permits direct use of (15)N relaxation rates, in the form of R(2)/R(1) ratios, as experimental restraints in structure calculations without requiring prior information to be extracted from a known molecular structure. The elements of the rotational diffusion tensor are calculated from the atomic coordinates at each step of the structure calculation and then used together with the N-H bond vector orientations to compute the (15)N R(2)/R(1) ratios. We show that the E(relax) term can be reliably used for protein-protein docking of complexes and illustrate its applicability to the 40 kDa complex of the N-terminal domain of enzyme I and the histidine phosphocarrier protein HPr and to the symmetric HIV-1 protease dimer.

Impact of 15N R2/R1 Relaxation Restraints on Molecular Size, Shape, and Bond Vector Orientation for NMR Protein Structure Determination with Sparse Distance Restraints

(15)N R(2)/R(1) relaxation data contain information on molecular shape and size as well as on bond vector orientations relative to the diffusion tensor. Since the diffusion tensor can be directly calculated from the molecular coordinates, direct inclusion of (15)N R(2)/R(1) restraints in NMR structure calculations without any a priori assumptions is possible. Here we show that (15)N R(2)/R(1) restraints are particularly valuable when only sparse distance restraints are available. Using three examples of proteins of varying size, namely, GB3 (56 residues), ubiquitin (76 residues), and the N-terminal domain of enzyme I (EIN, 249 residues), we show that incorporation of (15)N R(2)/R(1) restraints results in large and significant increases in coordinate accuracy that can make the difference between being able or unable to determine an approximate global fold. For GB3 and ubiquitin, good coordinate accuracy was obtained using only backbone hydrogen-bond restraints supplemented by (15)N R(2)/R(1) relaxation restraints. For EIN, the global fold could be determined using sparse nuclear Overhauser enhancement (NOE) distance restraints involving only NH and methyl groups in conjunction with (15)N R(2)/R(1) restraints. These results are of practical significance in the study of larger and more complex systems, where the increasing spectral complexity and number of chemical shift degeneracies reduce the number of unambiguous NOE assignments that can be readily obtained, resulting in progressively reduced NOE coverage as the size of the protein increases.

Fast-sol–gel derived silsequioxane glasses embodying glycerol moieties: dielectric properties and morphology

Abstract The fast-sol–gel synthetic route was utilized to prepare glassy matrices of varying porosity. Glycerol doping of these matrices was carried out at various stages of the sol–gel reaction. Dielectric spectroscopy data were collected from all these matrices, and interpreted in terms of various relaxation processes from which the internal morphology of the matrices could be deduced. Glycerol dopant added to the sol–gel-derived glass during preparation is adsorbed and partly chemically bound at the ends of the polymer-like chains of the matrix, acting as a cross-linking agent. It does not form bulk moieties at concentrations up to 2%. Cluster glycerol moieties are formed inside the glass at a concentration of 4%.

Spontaneous symmetry breaking in genome evolution

The quest for evolutionary mechanisms providing separation between the coding (exons) and noncoding (introns) parts of genomic DNA remains an important focus of genetics. This work combines an analysis of the most recent achievements of genomics and fundamental concepts of random processes to provide a novel point of view on genome evolution. Exon sizes in sequenced genomes show a lognormal distribution typical of a random Kolmogoroff fractioning process. This implies that the process of intron incretion may be independent of exon size, and therefore could be dependent on intron–exon boundaries. All genomes examined have two distinctive classes of exons, each with different evolutionary histories. In the framework proposed in this article, these two classes of exons can be derived from a hypothetical ancestral genome by (spontaneous) symmetry breaking. We note that one of these exon classes comprises mostly alternatively spliced exons.

Coupling between overall rotational diffusion and domain motions in proteins and its effect on dielectric spectra.

In this work, we formulate a closed‐form solution of the model of a semirigid molecule for the case of fluctuating and reorienting molecular electric dipole moment. We illustrate with numeric calculations the impact of protein domain motions on dielectric spectra using the example of the 128 kDa protein dimer of Enzyme I. We demonstrate that the most drastic effect occurs for situations when the characteristic time of protein domain dynamics is comparable to the time of overall molecular rotational diffusion. We suggest that protein domain motions could be a possible explanation for the high‐frequency contribution that accompanies the major relaxation dispersion peak in the dielectric spectra of protein aqueous solutions. We propose that the presented computational methodology could be used for the simultaneous analysis of dielectric spectroscopy and nuclear magnetic resonance data. Proteins 2015; 83:1571–1581.

Dielectric relaxation of water adsorbed on the pore surface of silica glasses

The dielectric relaxation properties of porous glass obtained from sodium borosilicate glass were studied by Dielectric Spectroscopy in the wide frequency (20 Hz÷1 MHz) and temperature (−100 °C÷+300 °C) ranges. The relaxation process which is well marked in the temperature range: −50 °C to +150 °C and has a specific saddle-like shape was considered. A simple model has been developed in order to explain the related anomalous behavior of the relaxation time as a function of temperature. The mechanism offered is related to a kinetic transition due to the water molecule reorientation in the vicinity of a defect.