The theory of ligand migration in biomacromolecules

A model for the process of ligand migration in bio-macromolecules is proposed. We assume that migration occurs by means of fluctuating creation of cavities in bio-macromolecules. A theory of particle migration through the fluctuating gap is created. The rate of migration is determined analytically for limiting cases. Theoretical results are applied to the migration of CO in myoglobin.     

Energization-induced redistribution of charge carriers near membranes

The electric field arising from proton pumping across a topologically closed biological membrane causes accumulation close to the membrane of ionic charges equivalent to the charge of the pumped protons, positive on the side towards which protons are pumped, negative on the other side. We shall call this the 'active surface charge'. We here use the Poisson-Boltzmann equation to evaluate the effects of zwitterionic buffer molecules and uncharged proteins in the aqueous phase bordering the membrane on the magnitude and ionic composition of the active surface charge. For the positive side of the membrane, the main results are: (1) If the membrane is freely accessible to bulk phase ions, pumped protons exchange with these ions, such that the active surface charge consists of salt cations. (2) If a significant fraction of the ions in bulk solution consists of buffer molecules, then some of the pumped protons will remain close to the membrane and constitute a major fraction of the active surface charge. (3) If a protein layer borders the membrane, a significant part of the transmembrane electric potential difference exists within that protein layer and protons inside this layer dominate the active surface charge. (4) On the negative side of the membrane the corresponding phenomena would occur. (5) All these effects are strictly dependent on the transmembrane electric potential difference arising from proton pumping and would come in addition to the well known effects of buffers and electrically charged proteins on the retention of scalar protons. (6) No additional proton diffusion barrier may be required to account for a deficit in number of protons observed in the aqueous bulk phase upon aeration-induced proton pumping.     

Dynamics of transfer of charge carriers in DNA molecule

An equivalent electrical circuit of DNA molecule is suggested and used to model the charge transfer dynamics in the molecule. Its switching time is shown to be in the femtosecond time range and to depend on the frequency of input electric signal. Raising the input signal frequency from 1 GHz to 4 THz and lowering the temperature decrease the current through DNA. The switching rate of DNA molecule is determined by the processes of delocalization and localization of holes, which is achieved by variation in the base sequence and length.     

Proton conduction in lecithins. III. Nature of charge carriers

The nature of charge carriers was studied in hydrated lecithin using different techniques. The current-voltage characteristics confirmed the ionic nature of conduction. Attempts to determine the charge mobility were unsuccessful. From measurements of the thermovoltage at different hydration levels the charge carrier was found to be positive. The value of the thermo electromotive force (thermo e.m.f.) depends on the phase state of the lipid but is independent of its water content. The mechanism of charge generation is discussed. The activation energy of conduction does not reflect the phase change directly. Its dependence on water content is attributed to charge mobility which involves the motion of the head groups. Electrolysis experiments were carried out and the amount of hydrogen evolved was determined by gas chromatography. A proton mechanism of conduction is suggested.     

Bond length pattern associated with charge carriers in armchair graphene nanoribbons

The geometry configuration of charged armchair graphene nanoribbons (AGNRs) is theoretically investigated in the framework of a two-dimensional tight-binding model that includes lattice relaxation. Our findings show that the charge distribution and, consequently, the bond length pattern is dependent on the parity of the nanoribbon width. In this sense, the lattice distortions decrease smoothly for increasingly wider GNRs. As should be expected, AGNRs belonging to a particular family present similar patterns for the bond lengths. The interplay between the electron-phonon coupling and band gap is also investigated. The results show that the electron-phonon coupling strength is fundamental to promote the transition from metallic towards semiconducting-like behavior for the band gap. Most important, such strength is crucial on defining the degree of lattice distortions in AGNRs.     

Polyamidoamine dendrimers with different surface charge as carriers in anticancer drug delivery

Second-generation (G2) polyamidoamine (PAMAM) dendrimers are branched polymers containing 16 surface primary amine groups. Due to their structural properties, these polymers can be used as universal carriers in various drug delivery systems. Amine-terminated PAMAM dendrimers are characterized by a high positive surface charge, leading to effective but nonspecific interactions with negatively charged cell plasmatic membranes. To reduce the nonspecific internalization of PAMAM dendrimers, their primary amine groups are often modified by acetic or succinic anhydrides, polyethylene glycol derivatives and other compounds. In this work, the role of primary amine groups, which are localized on the surface of doxorubicin-conjugated (Dox) dendrimers, was studied with regard to their intracellular distribution and internalization rates using SKOV3 human ovarian adenocarcinoma cells. It was demonstrated that all Dox-labeled G2-derivatives containing different numbers of acetamide groups synthesized in this work show high rates of cellular uptake at 37°С. As expected, the conjugate carrying the maximum number of primary amine groups demonstrated the highest rates of binding and endocytosis. At the same time, the G2-Dox conjugate containing the maximum number of acetamide groups showed colocalization with LAMP2, a marker of lysosomes and late endosomes, as well as the highest level of cytotoxic activity against SKOV3 cells. We conclude that second-generation PAMAM dendrimers are characterized by varied pathways of internalization and intracellular distribution due to the number of primary amine groups on their surface and, as a consequence, a different surface charge.     

The conformational free-energy map for solvated neocarrabiose

A Ramachandran map of the conformational potential of mean force (pmf) for neocarrabiose in water was obtained using molecular dynamics (MD) simulations with umbrella sampling. The potential energy map calculated in a previous study for this molecule in vacuum exhibited a global minimum located at (phi = 81 degrees, psi = -141 degrees). However, the global minimum on the new pmf map in aqueous solution is located in an area centered around (phi = 175 degrees, psi = 180 degrees), indicating a considerable solvent shift. This new global minimum-energy solution conformation was found to correspond to the experimental value obtained from NMR-NOE measurements, and is also consistent with the experimental crystal structure for neocarrabiose and the fiber diffraction conformation for iota-carrageenan. The global minimum of the solution pmf and its local topology were found to be approximately reproduced by quick vacuum conformational energy mapping using several approximations that mimic solvation effects by de-emphasizing intramolecular hydrogen bonding.     

Sodium ions as blocking agents and charge carriers in the potassium channel of the squid giant axon

Instantaneous K channel current-voltage (I-V) relations were determined by using internally perfused squid axons. When K was the only internal cation, the I-V relation was linear for outward currents at membrane potentials up to +240 mV inside. With 25-200 mM Na plus 300 mM K in the internal solution, an N-shaped I-V curve was seen. Voltage-dependent blocking of the K channels by Na produces a region of negative slope in the I-V plot (F. Bezanilla and C. M. Armstrong. 1972. J. Gen Physiol, 60: 588). At higher voltages (greater than or equal to 160 mV) we observed a second region of increasing current and a decrease in the fraction of the K conductance blocked by Na. Internal tetraethylammonium (TEA) ions blocked currents over the whole voltage range. In a second series of experiments with K-free, Na-containing internal solutions, the I-V curve turned sharply upward about +160 mV. The current at high voltages increased with increasing internal Na concentration was largely blocked by internal TEA. These data suggest that the K channel becomes substantially more permeable to Na at high voltages. This change is apparently responsible for the relief, at high transmembrane voltages, of the blocking effect seen in axons perfused with Na plus K mixtures. Each time a Na ion passed through, vacating the blocking site, the channel would transiently allow K ions to pass through freely.     

Long-range distance determinations in biomacromolecules by EPR spectroscopy

Electron paramagnetic resonance (EPR) spectroscopy provides a variety of tools to study structures and structural changes of large biomolecules or complexes thereof. In order to unravel secondary structure elements, domain arrangements or complex formation, continuous wave and pulsed EPR methods capable of measuring the magnetic dipole coupling between two unpaired electrons can be used to obtain long-range distance constraints on the nanometer scale. Such methods yield reliably and precisely distances of up to 80 A, can be applied to biomolecules in aqueous buffer solutions or membranes, and are not size limited. They can be applied either at cryogenic or physiological temperatures and down to amounts of a few nanomoles. Spin centers may be metal ions, metal clusters, cofactor radicals, amino acid radicals, or spin labels. In this review, we discuss the advantages and limitations of the different EPR spectroscopic methods, briefly describe their theoretical background, and summarize important biological applications. The main focus of this article will be on pulsed EPR methods like pulsed electron-electron double resonance (PELDOR) and their applications to spin-labeled biosystems.     

Quinolone effects in the SOS chromotest and in the synthesis of biomacromolecules

The genotoxicity of quinolone antibiotics (ciprofloxacin, enoxacin, nalidixic acid, norfloxacin, ofloxacin, pefloxacin) was studied on the selected mutantE. coli strain PQ37 (SOS chromotest). The genotoxicity was expressed by SOS-inducing potential (SOSIP) values. The highest SOSIP values were found with ciprofloxacin (SOSIP=1967 δIF/nmol), the lowest value was observed with nalidixic acid (SOSIP=0.3 ΔIF/nmol). Similar results were also found with the biosynthesis of nucleic acids, as indicated by incorporation of¹⁴C-adenine into TCA-insoluble fractions ofS. typhimurium cells (ciprofloxacin IC₅₀=0.39, nalidixic acid IC₅₀=400). DNA-damaging effects were tested in the absence of an exogenous metabolizing system.     

Bioproduction of biomacromolecules for antiviral applications

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