Molecular structure and the dynamics of the functioning of conformationally mobile systems

The state of art of research on the dynamics of biomacromolecules and complexes thereof is briefly outlined. Emphasis is placed on the work conduced over the last 30 years at Lomonosov Moscow State University and Semenov Institute of Chemical Physics RAS. The physical mechanisms of fluctuation dynamics on the angstrom and subangstrom levels in condensed matter are considered based on Mössbauer spectroscopy and molecular dynamics modeling. The results of all-atom simulations of the functioning of ion channels obtained on a “Lomonosov” supercomputer (MSU) are reported. The self-organizing dynamics of macromolecular structures is examined for model polymer structures and nanostructures. The topology of multidimensional energy surfaces for conformationally mobile systems and its influence on the dynamic properties of objects are considered. In conclusion, the dynamics of functioning of simple molecular machines based on catenanes and rotaxanes and the role of conformational mobility in ensuring their operation are discussed.     

Modification of magnetic anisotropy in metallic glasses using high-energy ion beam irradiation

Heavy ion irradiation in the electronic stopping power region induces macroscopic dimensional change in metallic glasses and introduces magnetic anisotropy in some magnetic materials. The present work is on the irradiation study of ferromagnetic metallic glasses, where both dimensional change and modification of magnetic anisotropy are expected. Magnetic anisotropy was measured using Mössbauer spectroscopy of virgin and irradiated Fe₄₀Ni₄₀B₂₀ and Fe₄₀Ni₃₈Mo₄B₁₈ metallic glass ribbons. 90 MeV ¹²⁷I beam was used for the irradiations. Irradiation doses were 5×10¹³ and 7.5×10¹³ ions/cm². The relative intensity ratios D ₂₃ of the second and third lines of the Mössbauer spectra were measured to determine the magnetic anisotropy. The virgin samples of both the materials display in-plane magnetic anisotropy, i.e., the spins are oriented parallel to the ribbon plane. Irradiation is found to cause reduction in magnetic anisotropy. Near-complete randomization of magnetic moments is observed at high irradiation doses. Correlation is found between the residual stresses introduced by ion irradiation and the change in magnetic anisotropy.     

A model for short alpha-neurotoxin bound to nicotinic acetylcholine receptor from Torpedo californica: comparison with long-chain alpha-neurotoxins and alpha-conotoxins

Short-chain alpha-neurotoxins from snakes are highly selective antagonists of the muscle-type nicotinic acetylcholine receptors (nAChR). Although their spatial structures are known and abundant information on topology of binding to nAChR is obtained by labeling and mutagenesis studies, the accurate structure of the complex is not yet known. Here, we present a model for a short alpha-neurotoxin, neurotoxin II from Naja oxiana (NTII), bound to Torpedo californica nAChR. It was built by comparative modeling, docking and molecular dynamics using 1H NMR structure of NTII, cross-linking and mutagenesis data, cryoelectron microscopy structure of Torpedo marmorata nAChR [Unwin, N., 2005. Refined structure of the nicotinic acetylcholine receptor at 4A resolution. J. Mol. Biol. 346, 967-989] and X-ray structures of acetylcholine-binding protein (AChBP) with agonists [Celie, P.H., van Rossum-Fikkert, S.E., van Dijk, W.J., Brejc, K., Smit, A.B., Sixma, T.K., 2004. Nicotine and carbamylcholine binding to nicotinic acetylcholine receptors as studied in AChBP crystal structures. Neuron 41 (6), 907-914] and antagonists: alpha-cobratoxin, a long-chain alpha-neurotoxin [Bourne, Y., Talley, T.T., Hansen, S.B., Taylor, P., Marchot, P., 2005. Crystal structure of Cbtx-AChBP complex reveals essential interactions between snake alpha-neurotoxins and nicotinic receptors. EMBO J. 24 (8), 1512-1522] and alpha-conotoxin [Celie, P.H., Kasheverov, I.E., Mordvintsev, D.Y., Hogg, R.C., van Nierop, P., van Elk, R., van Rossum-Fikkert, S.E., Zhmak, M.N., Bertrand, D., Tsetlin, V., Sixma, T.K., Smit, A.B., 2005. Crystal structure of nicotinic acetylcholine receptor homolog AChBP in complex with an alpha-conotoxin PnIA variant. Nat. Struct. Mol. Biol. 12 (7), 582-588]. In complex with the receptor, NTII was located at about 30 A from the membrane surface, the tip of its loop II plunges into the ligand-binding pocket between the alpha/gamma or alpha/delta nAChR subunits, while the loops I and III contact nAChR by their tips only in a 'surface-touch' manner. The toxin structure undergoes some changes during the final complex formation (for 1.45 rmsd in 15-25 ps according to AMBER'99 molecular dynamics simulation), which correlates with NMR data. The data on the mobility and accessibility of spin- and fluorescence labels in free and bound NTII were used in MD simulations. The binding process is dependent on spontaneous outward movement of the C-loop earlier found in the AChBP complexes with alpha-cobratoxin and alpha-conotoxin. Among common features in binding of short- and long alpha-neurotoxins is the rearrangement of aromatic residues in the binding pocket not observed for alpha-conotoxin binding. Being in general very similar, the binding modes of short- and long alpha-neurotoxins differ in the ways of loop II entry into nAChR.     

Steered molecular dynamics simulations of cobra cytotoxin interaction with zwitterionic lipid bilayer: no penetration of loop tips into membranes

Cobra cytotoxins, small proteins of three-fingered toxin family, unspecifically damage membranes in different cells and artificial vesicles. However, the molecular mechanism of this damage is not yet completely understood. We used steered molecular dynamics simulations to study the interaction of cardiotoxin A3 from Naja atra cobra venom with hydrated 1-palmitoyl-2-oleoyl-1-sn-3-phosphatidylcholine (POPC) bilayer. The studied system included one cytotoxin molecule, 64 lipid molecules (32 molecules in each monolayer) and 2500 water molecules. It was found that the toxin interacted with zwitterionic bilayer formed by POPC. During first nanosecond of simulation the toxin molecule was oriented toward membrane surface by loops' basement including cytotoxin regions Cys14-Asn19 and Cys38-Ser46. This orientation was stable enough and was not changed during next 6 ns of simulation. The obtained data suggest that cytotoxin molecule cannot penetrate into membrane composed of zwitterionic lipids without some auxiliary interaction.     

Magnetization curves for general cylindrical samples in a transverse field

Using the recent results for the surface current density on cylindrical surfaces of arbitrary cross-section producing uniform interior magnetic field we propose a method for obtaining solutions of Bean’s critical state model for general cylindrical samples. The method uses the technique of conformal mapping to express the sample surface and the flux-fronts in terms of a set of coefficients that depend on a parameter. The flux-fronts are to be determined by solving a system of nonlinear ordinary differential equations for the coefficients. Retaining only a certain finite number of leading coefficients we get an approximate solution. The procedure is illustrated by considering two cyclindrical samples — one with an elliptical cross-section and the other with a non-elliptical cross-section. The virgin curve and small and large magnetization hysteresis loops for the two samples are obtained.     

Energy Surface and Conformation Dynamics of Molecules

The topology of energy surfaces and the dynamics of conformationally-labile molecules are discussed. A base model is introduced for an ideal lattice on a multidimensional torus for the energy level surfaces of rotational-isomeric chains. Specific features of the dynamics of molecules of various types are discussed, together with the problems of the formation of a three-dimensional structure and the link between the conformational mobility and the chemical act of reactions.     

Low-field vortex dynamics in various high-T c thin films

We present a novel ac susceptibility technique for the study of vortex creep in superconducting thin films. With this technique we study the dynamics of dilute vortices in c-axis oriented Y-123, Hg-1212, and Tl-1212 thin films, as well as a axis oriented Hg-1212 thin films. Results on the Hg-1212 and Tl-1212 thin films indicate that dislocation-mediated plastic flux creep of single vortices dominates at low temperatures and fields. As the temperature (or the field) is increased, the increasing vortex-vortex interactions promote a collective behavior, which can be characterized by elastic creep with a non-zero μ exponent. Also, in some of these samples effects of thermally assisted quantum creep are visible up to 45 K in some of these samples. In Y-123 thin films, creep is found to be collective down to the lowest temperatures and fields investigated, while the quantum creep persists only up to 10–11 K.     

Synthetic magnetic opals

We present studies of novel nanocomposites of BiNi impregnated into the structure of opals as well as inverse opals. Atomic force microscopy and high resolution elemental analyses show a highly ordered structure and uniform distribution of the BiNi filler in the matrix. These BiNi-based nanocomposites are found to exhibit distinct ferromagnetic-like ordering with transition temperature of about 675 K. As far as we know there exists no report in literature on any BiNi compound which is magnetic.     

Biocrystallization of bacterial nucleoid under stress

Structural, biochemical, and genetic changes caused by stress factors are known to be largely similar for cells of all modern organisms, which inherited the basic strategies of adaptation to different types of stress from their ancient ancestors. In the present work, the adaptation process is considered for the simplest example of the bacterial E. coli nucleoid. Experimental studies performed recently on prokaryotic bacterial cells, the simplest living organisms, have demonstrated that, under unfavorable environmental conditions (for example, starvation), bacterial cells can use biocrystallization, a special mechanism of protection of the genetic apparatus (nucleoid), generally untypical of living organisms. This mechanism helps to protect the nucleoid from damage and resume the activity of the bacterial cells later, upon improvement of the external conditions. The results of studying the structure of the nucleoid of E. coli bacteria (BL21-Gold strain (DE3)) subjected to starvation stress by using synchrotron radiation at the ESRF beamline ID23-1 are reported.