Yury M. Romanovsky

ROTATION OF F1-ATPASE: THE STOCHASTIC MODEL

In this work, we consider a stochastic model describing the unidirectional rotation of the rotor (subunit γ) of F1-ATPase. For appropriate choice of the model parameters, we used literature data on dynamic parameters of F1-ATPase and results of our calculations of electrostatic interactions in enzyme-substrate complex of the catalytic cycle. The model takes into account thermal fluctuations of the bath and stochastic processes of substrate binding and product dissociation from the catalytic centers. The model provides an adequate description of ATP-driven rotations of subunit in F1-ATPase.

Computer simulation of the decay of nonlinear subglobular oscillations in aqueous solutions of protein molecules

The efficiency of the molecular machines can be determined by the Q-factor of oscillations in the selected degrees of freedom. In particular, the quasi-harmonic oscillations of chymotrypsin decrease the threshold for the diffusion limitation of its functioning as molecular scissors. It was demonstrated by the methods of molecular dynamics that the Q-factor of the subglobular oscillations of proteins in water at the frequencies (omega) about 1012 Hz can reach 10, although the Raman bands in the corresponding spectral range were found only in crystal samples. Q quadratically increases with (omega) . The earlier hypothesis regarding the catalytic importance of the Fermi resonance for the oscillations of ligands and atomic groups in the enzyme- substrate complexes was not proved in experiments with simple models. The Fermi resonance can be observed if the Q- factor of the selected degree of freedom exceeds 100.

Stochastic dynamics of enzymes - "molecular scissors

The problems studied here are relevant for an understanding of the functioning of hydrolytic enzyme molecules. These enzymes work like molecular machines breaking off the valence peptid bonds of substrates. In particular the role of Fermi resonance which is evident from a spectral lines of valence oscillations is studied. The influence of this resonance on valence splitting is discussed. It is shown that the breaking of these bonds has a higher probability, if the stochastic oscillations of atoms in catalytic groups at the active site have a large quality coefficient. We show that the corresponding low damping is essential for the Fermi resonance modes of these oscillations.

Functional dynamics of hydrolytic enzymes

One of important stages of the substrate bond breaking in the active site (AS) of α-chymotrypsin (ACT) is considered. Three tasks are solved by methods of quantum mechanics and stochastic molecular dynamics: the loosening of peptide bond of a substrate attacked by O- ion of Ser195 of catalytic group; the opportunity of increase of a peptide bond (PB) breaking probability; the increase of this probability related to nonlinear interacting modes (or Fermi resonance (FR)) of oscillations of group N-H in PB. It is shown also that the splitting of vibrational levels Amide A and Amide B in a spectrum of an amide group pays off due to FR.

Electrostatic interactions in catalytic centers of F 1 -ATPase

F1-ATPase is one of the most important enzymes of membrane bioenergetics. F1-ATPase is the constituent complex that provides the ATP formation from ADP and inorganic phosphate (Pi) at the expense of energy of electrochemical gradient of hydrogen ions generated across the energy transducing mitochondrial, chloroplast or bacterial membrane. F1-ATPase is a reversible molecular machine that can work as a proton pump due to energy released in the course of ATP hydrolysis (ATPase reaction). The unusual feature of this enzyme is that it operates as a rotary molecular motor. Recently, using the fluorescence microscopy method for the real time visualization of molecular mobility of individual molecules, it was demonstrated directly that the ATP hydrolysis by F1-ATPase is accompanied by unidirectional rotations of mobile subunits (rotor) of F1F0-ATP synthase. In this work, we calculated the contribution of electrostatic interactions between charged groups of a substrate (MgATP), products molecules (MgADP and Pi), and charged amino acid residuals of ATPase molecule to the energy changes associated with the substrate binding and their chemical transformations in the catalytic centers located at the interface of α and β subunits of the enzyme (oligomer complex α3β3γ of bovine mitochondria ATPase). A catalytic cycle of ATP hydrolysis considered in our work includes conformational changes of α and β subunits caused by unidirectional rotations of an eccentric γ subunit. The knowledge of energy characteristics and force field in catalytic center of an enzyme in different conformational states may be important for further simulation dynamic properties of ATP synthase complex.

Propagating of bioelectric potentials in green plants' conducting system: mathematical modeling and experiment

Propagation of bioelectric potentials generated in green plants by light and millimeter wavelength range irradiation was experimentally investigated. The standard technique of multi-electrode superficial potentials measuring was used. The carried out experiments continue the previous investigations of light and millimeter waves influence on green plants. Theoretical part includes the development of numerical models of bioelectric potentials propagation and measurement.

Are the subglobular oscillations of protein molecule in water overdamped

Raman spectra of crystalline subglobular proteins exhibit peaks in the low-frequency spectral range. These peaks can be related to resonance oscillations of subglobules and possibly play an important role in the catalytic act. The low-frequency spectral features were not observed in aqueous solutions. According to the hydrodynamics, the corresponding oscillations must be overdamped. The results obtained by the methods of molecular dynamics how that the Q-factor of subglobular oscillations can be larger than 10, which stimulated further experimental studies of solutions of proteins.

Complex regimes of the contractile activity in Physarum plasmodium: laser diagnostics of intracellular flows and mathematical models

The intracellular motility of the huge amoeboid cell, Physarum plasmodium, is defined by autowave processes, which are caused by interaction of actomyosin-based contractile apparatus in ectoplasm and intracellular endoplasmic flows. With the use of cell tensiometry and laser Doppler spectroscopy technique the autowave regimes in plasmodial strands (which look like blood-vessels) was investigated under the conditions when endogenous contractile rhythm in a part of the strand was eliminated by respiratory inhibitors. Mathematical model for ectoplasm contraction waves and shuttle endoplasm streaming in the strand is presented. Solutions of the model expanded to simulate the case of non- uniform parameter distribution satisfactorily agree with the experimentally observed effects of the respiratory inhibitors.

Physical and mathematical models of the heat action of laser radiation on biotissues

A mathematical model of contact laser destruction of normal and tumor liver tissues by radiation of YAG:Nd laser is described. We present the results of the simulation of tissue heat destruction, taking into account the influence of blood and lymph circulation on the processes of heat transfer. The problem is adapted to the case of liver tissue with tumor. A liver is considered as a capillary-porous body with internal blood circulation. Heatconductivity and tissue-blood heat transfer are considered. Heat action is assumed to be implemented with contact laser scalpel. The mathematical model consists of two inhomogeneous nonlinear equations of heatconductivity with spherical symmetry. Nonstationary temperature fields of tissue and blood are determined. The power of laser radiation (LR) was taken into account in boundary conditions set for the center of coagulated tissue volume. We also took into account the processes connected with changing of substance phase (vaporization). The original computer programs allow one to solve the problem varying in a wide range of the main parameters. Reasonable agreement was found between the calculation results and the experimental data for operations on macrosamples and on test animals.

Generation of bioelectric potentials in green plants by low-intensity local electromagnetic excitation in the range from 380 nm to 6 mm

Bioelectric plant reactions induced by local low-intensity electromagnetic millimeter wavelength excitation were studied; the results are presented in this article. Plant reaction was obtained in this range where the absorption is determined by collective resonant properties of water. As a result, the previous investigations were continued and we can present the action spectrum in the range 300 nm-6mm.