Milan Melicherčík

Oscillatory oxidation of Mn(II) ions by hexacyanoferrates(III) and bistability in the reductions of MnO2 by hexacyanoferrates(II) in a CSTR

Abstract A new transition metal oscillator based on the oxidation of Mn2+ ions by Fe(CN)3−6 ions in a CSTR has been found. As well as the oscillations of the absorbance of the Mn(IV) species, pH-oscillations have been observed. In the reduction of manganese dioxide by Fe(CN)4−6 ions a kinetic bistability has been described. A skeleton mechanism described recently for Mn(II)H2O2 and Mn(II)Br2 oscillators has been applied here and further developed by the idea of the catalytic activity of colloidal particles and of the assistance of the pH-value change of both main processes, i.e. of the Mn(II) oxidation by Fe(CN)3−6 ions and of the Mn(IV) reduction by Fe(CN)4−6 ions. This appears to be the first case where both sides of a reversible reaction are autocatalytic.

Symmetric Allosteric Mechanism of Hexameric Escherichia coli Arginine Repressor Exploits Competition between L-Arginine Ligands and Resident Arginine Residues

An elegantly simple and probably ancient molecular mechanism of allostery is described for the Escherichia coli arginine repressor ArgR, the master feedback regulator of transcription in L-arginine metabolism. Molecular dynamics simulations with ArgRC, the hexameric domain that binds L-arginine with negative cooperativity, reveal that conserved arginine and aspartate residues in each ligand-binding pocket promote rotational oscillation of apoArgRC trimers by engagement and release of hydrogen-bonded salt bridges. Binding of exogenous L-arginine displaces resident arginine residues and arrests oscillation, shifting the equilibrium quaternary ensemble and promoting motions that maintain the configurational entropy of the system. A single L-arg ligand is necessary and sufficient to arrest oscillation, and enables formation of a cooperative hydrogen-bond network at the subunit interface. The results are used to construct a free-energy reaction coordinate that accounts for the negative cooperativity and distinctive thermodynamic signature of L-arginine binding detected by calorimetry. The symmetry of the hexamer is maintained as each ligand binds, despite the conceptual asymmetry of partially-liganded states. The results thus offer the first opportunity to describe in structural and thermodynamic terms the symmetric relaxed state predicted by the concerted allostery model of Monod, Wyman, and Changeux, revealing that this state is achieved by exploiting the dynamics of the assembly and the distributed nature of its cohesive free energy. The ArgR example reveals that symmetry can be maintained even when binding sites fill sequentially due to negative cooperativity, which was not anticipated by the Monod, Wyman, and Changeux model. The molecular mechanism identified here neither specifies nor requires a pathway for transmission of the allosteric signal through the protein, and it suggests the possibility that binding of free amino acids was an early innovation in the evolution of allostery.

Oscillatory System I―, H2O2, HClO4: The Modified Form of the Bray-Liebhafsky Reaction

The kinetics of iodide ions oxidation with hydrogen peroxide in solutions of perchloric acid at temperature of 60 degrees C has been studied in detail. We have found conditions under which this reaction proceeds oscillatory. The Bray-Liebhafsky (BL) oscillatory reaction started by the oxidation of iodide ions with hydrogen peroxide is described for the first time. The described results support our assumption (Olexová, A.; Mrákavová, M.; Melichercík, M.; Treindl, L. Collect. Czech. Chem. Commun. 2006, 71, 91-106) that singlet oxygen ((1)O(2)) is an important intermediate of the BL oscillatory reaction in the sense of the Noyes-Treindl (N-T) skeleton mechanism (Treindl, L.; Noyes, R.M. J. Phys. Chem. 1993, 97, 11354-11362).

Kinetics of the oxidation of iodine by hydrogen peroxide catalyzed by MoO2−4 ions

Abstract The kinetics of the oxidation of iodine by hydrogen peroxide catalyzed by MoO2−4 ions with a ‘clock’ behaviour is described and the corresponding reaction scheme is proposed. The ‘clock’ behaviour is explained by the assumption that the oxidation of iodine cannot proceed until the iodide concentration drops to a certain treshold, since this reaction can only through the HOI species proceed. The noncatalyzed, direct oxidation of iodine by H2O2 is too slow to become one of the main two processes of the Bray-Liebhafsky oscillatory reaction.

Synergy of Molecular Dynamics and Isothermal Titration Calorimetry in Studies of Allostery

Despite decades of intensive study, allosteric effects have eluded an intellectually satisfying integrated understanding that includes a description of the reaction coordinate in terms of species distributions of structures and free energy levels in the conformational ensemble. This chapter illustrates a way to fill this gap by interpreting thermodynamic and structural results through the lens of molecular dynamics simulation analysis to link atomic-level detail with global response. In this synergistic approach molecular dynamics forms an integral part of a feedback loop of hypothesis, experimental design, and interpretation that conforms to the scientific method.

Chemical oscillators based on the oxidation of Mn(II) by some halogens

Chemical oscillators based on the oxidation of Mn(II) ions by bromine or chlorine in NaH2PO4−NaOH buffer solutions in a CSTR (continuous-flow stirred tank reactor) are described. The oscillations correspond to the two alternating processes. The first process is the oxidation of Mn(II) by HOBr or HOCl to Mn(IV) and the second one is of a micro-heterogeneous nature, consisting of the reduction of Mnc4+ and Mnc3+ centers on the surface of colloids (MnO2)col by halides.

Effect of the aminoacid composition of model α-helical peptides on the physical properties of lipid bilayers and peptide conformation: a molecular dynamics simulation

The interaction of a model Lys flanked α-helical peptides K2-X24-K2, (X = A,I,L,L+A,V) with lipid bilayers composed of dimyristoylphosphatidylcholine (DMPC) and dipalmitoylphosphatidylcholine (DPPC) both, in a gel and in a liquid-crystalline state, has been studied by molecular dynamics simulations. It has been shown that these peptides cause disordering of the lipid bilayer in the gel state but only small changes have been monitored in a liquid-crystalline state. The peptides affect ordering of the surrounding lipids depending on the helix stability which is determined by amino acid side chains – their volume, shape, etc. We have shown that the helix does not keep the linear shape in all simulations but often bends or breaks. During some simulations with a very small difference between hydrophobic length of peptide and membrane thickness the peptide exhibits negligible tilt. At the same time changes in peptide conformations during simulations resulted in appearance of superhelix.

The ferroin-catalyzed Belousov-Zhabotinskii system with a “clock” behaviour

Abstract The ferroin-catalyzed Belousov-Zhabotinskii oscillatory system with methyl-, ethyl-, or isopropyl-ester of 3-oxobutanoic acid exhibits a “clock” behaviour and subsequent two-frequency oscillations. The influence of oxygen on the “clock” behaviour is assumed to be caused by an interaction of oxygen as a scavenger with intermediary radicals. A mechanism of the “clock” behaviour together with two-frequency oscillations of the Belousov-Zhabotinskii type will be developed later.

Molecular Dynamics Simulations of Lipid Bilayers with Incorporated Peptides

Biological membranes are important cell structures that play important role in the transport of the ions and other molecules into and out of the cell and regulate the signaling pathway. They are composed of lipid bilayer, integral and peripheral proteins. The ionic channels, enzymes and most of the membrane receptors belong to integral proteins that span the membrane and contact by their hydrophobic part with hydrophobic interior of the lipid bilayer. These hydrophobic interactions are crucial for the effect of peptide on a lipid bilayer matrix and vice versa. The study of the mechanisms of these interactions is important for understanding the functioning of the peptides in a membrane. However the study of native biomembrane is rather complicated due to its complexity and inhomogeneity. Therefore model lipid bilayers and short peptides can be used as a model for study of the protein–lipid interactions. In this chapter we review the current state of the art in experimental and molecular dynamics simulation study of the short peptide–membrane interactions. As an example we consider in more detail the application of molecular dynamic simulations on the study of interaction of a model lysine-flanked α-helical peptides P24, LA12, L24 and its analogues A24, I24, and V24 with lipid bilayers composed of dimyristoylphosphatidylcholine (DMPC) and dipalmitoylphosphatidylcholine (DPPC) both in a gel and in a liquid-crystalline state. We have shown that these peptides cause disordering of the lipid bilayer in the gel state and small changes in a liquid-crystalline state. The peptides affect ordering of the surrounding lipids depending on the helix stability, the amount of dihedral angles in trans conformation and the number of transitions between trans and gauche conformation. It has been found the tendency of Lys-flanked peptides to compensate the positive mismatch between peptide and membrane hydrophobic core by tilting. In some cases the tilt was replaced by superhelical double-twisted structure. The rest of helices were bend or produced kink in addition to the tilt. The lipid structural state around the peptide has been also analyzed.

DFT and MD study of the divalent-cation-mediated interaction of ochratoxin A with DNA nucleosides

Aptamers are ligand-binding nucleic acids with affinities and selectivities that make them useful for the detection of a variety of compounds, including ochratoxin A. Theoretical methods can be applied to study the recognition interaction between aptamers and the ochratoxin A molecule. In this work, molecular dynamics simulations and quantum chemical calculations performed at the DFT level of theory were used to study the structures and energies of aptamers and aptamer–ochratoxin A complexes. The optimal structures as well as the interaction energies of these structures were elucidated. Divalent cations in the water solvent were shown to be an important influence on the structures and stabilities of the complexes.