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The fundamental criteria of the quality of molecular dynamics (MD) simulation represent a pivotal challenge, especially in the case of MD simulations of large systems (in particular, proteins).This work presents a simple theoretical analysis of time reversibility in classical mechanics that has allowed us to formulate a number of constructive criteria for evaluating the quality of the trajectories, generated in MD simulations. The results of testing the criteria on the structures of eight small proteins are presented. The criteria can be useful for solving different MD problems, such as: choosing the most appropriate thermostats for a MD system under study, the methods for sampling conformations, etc.Communicated by Ramaswamy H. Sarma.

It is known that in quantum mechanics the act of observing the experiment can affect the experimental findings in some cases. In particular, it happens under the so-called Zeno effect. In this work it is shown that in contrast to the "standard" Zeno-effect where the act of observing a process reduces the probability of its reality, an inverse situation when a particle transmits through a potential barrier (a so-called barrier anti-Zeno effect) can be observed, the observation of the particle essentially increases the probability of its transmission through the barrier. The possibility of using the barrier anti-Zeno effect is discussed to explain paradoxical results of experiments on "cold nuclear fusion" observed in various systems including biological ones. (According to the observers who performed the observations, the energy generation, which could not be explained by any chemical processes, as well as the change in the isotope and even element composition of the studied object may occur in these systems.

Coherent sources of electromagnetic waves in the terahertz frequency range are very promising for various applications, including biology and medicine. In this paper we propose a scheme of a compact terahertz source, in which terahertz radiation is generated due to effective interaction of electrons in a quantum well with an electromagnetic wave of a corrugated waveguide. We have shown that the generation of electromagnetic waves with a frequency of 1012 sec(-1) and an output power of up to 25. mW is possible in the proposed scheme.

The analysis of conformationally stable (conformational conservative) tetrapeptides selected from protein structures deposited in PDBSelect data bank has been fulfilled. The subset contained 943 tetrapeptide amino acid sequences and there were merely five 3D protein segment representatives for each sequence. As a result, the conclusion has been drawn on the basis of DSSP annotation analysis that in the majority of cases (900 of 943) alpha-helical conformation is obvious. Different than alpha-helix, in particular, the left-handed polyproline II helical conformation was observed in 43 sequences. The physical and chemical properties of conformationally stable peptides taken from the appropriate sample were estimated by the average hydrophobicity/hydrophilicity of tetrapeptides. The results of calculations show that the "neutrality" towards hydrophobicity/hydrophilicity is representative of conformationally stable oligopeptides. It should be noted, that dispersion of hydrophobicity/hydrophilicity distribution is sufficiently lower than for the test subsets. Thus, the conformationally stable oligopeptides present a distinct group of local protein structures which are very close with respect to conformational and physicochemical properties. In accordance with our developed theory of specific long range interactions these peptides are the objects being quite useful for effective mutual molecular recognition.

During experimental studies of thermal regime of female mammary glands tissues the existence of periodic thermal waves was discovered. At the same time, the space-amplitude relief of such waves can mask the space-amplitude relief of the thermal profile, projected to the skin surface of mammary glands by tumor, hidden in the thickness of the gland. The phenomenon observed would be taken into account upon diagnosing pathological states of mammary glands.

We propose a method for magnetic sorting of cell suspensions able to differentiate not only cells with single specific antigen on their surface, but also cells with a group of pre-defined antigens. Individually, each antigen of this group may be present on surfaces of non-selected cells. However, only the simultaneous presence of all given antigens on the cell surface means that such a cell should be separated. The method is of interest, for purification of cell suspensions from malignant cells, in particular, for purification of bone marrow material for autologous transplantation in leukemia.

Spheroid cell structures in the cell cultures have been described and are used for studying cell-cell and cell- matrix interactions. At the same time, spheroid cell structure participation in the repair and development of cancer in vivo remains unexplored. The aim of this study was to investigate the cellular composition of spherical structures and their functional significance in the repair of squamous epithelium in human papilloma virus-associated cervical pathology--chronic cervicitis and cervical intraepithelial neoplasia 1-3 degree, and also construct a mathematical model to explain the development and behavior of such spheroid cell structure.

When using nanodevices in oncology, it is necessary to provide the efficiency of the performance of these nanodevices simultaneously with their safety for an organism. These are conflicting objectives to some extent. Nevertheless, as shown in this work, an approach that helps to eliminate this contradiction is offered. For recognition and destruction of cancer cells in vivo it is suggested to use instead of one type simultaneously two types of introduced into an organism specialized nanodevices interacting with each other. Some of the nanodevices only recognize cancer cells, while the other ones, that can not recognize them, find cells being marked by nanodevices of the first type, and destroy them. This makes possible to increase the reliability of the cancer cell recognition process on the one side, and have the process of their destruction rather safe for an organism on the other side.

In the work the arguments are presented in favor of the idea on the role of conformationally stable oligo-peptides in specific long-distance interactions in phenomena of molecular recognition during various biological processes. Original authors' and literature data are taken into account. The examples of conformationally stable short oligopeptides participation in alpha-helix and collagen type structures formation are given simultaneously with theoretical approaches. The conformationally stable oligopeptides obtained in the course of PDB bank analysis are discussed. The role of amino acids sequence in collagen helix formation is shown.

A fundamentally new recognition method of bio-objects (in particular malignant cells) that escape the immune system supervision control is suggested. Recognition of such bio-objects should be carried out by the unified complex consisting of several molecular groups (for example, antibodies) bound to each other, each group identifies on a surface of this bio-object its target binding site. The choice of such targets is determined by a specific surface-antigen expression profiling. Thus the efficiency of recognition appears to be many times higher, than that in a situation when these molecular groups do not form a uniform complex and operate separately. The possibilities of destruction of such recognized cells are discussed.

It was shown that selective interactions between helical segments of macromolecules can realize in globular proteins in the segments characterized by the same periodicities of charge distribution i.e. between conformationally conservative oligopeptides. It was found that in the macromolecules of alpha-helical proteins conformationally conservative oligopeptides are disposed at a distance being characteristic of direct interactions. For representatives of many structural families of alpha-type proteins specific disposition of conformationally conservative segments is observed. This disposition is inherent to a particular structural family. Disposition of conformationally conservative segments is not related to homology of the amino acid sequence but reflects peculiarities of native 3D-architectures of protein globules.

On the basis of the theory of specific long-range interaction between long molecules the approach has been elaborated for the "fast reading" of nucleotide sequences in sole DNA molecule. Firstly, a stretching force applies to the molecule that causes its unwinding from B-form to so called S-form. Then, a molecule disposes in a stretched state on the background. After this, the electrostatic potential is estimated in the space along the DNA filament. Information obtained is sufficient for the deduction of the nucleotide sequence in DNA. Another approach to the "reading" of information reduces to the measurement of the filament element deformation induced by electrostatic field from the electrode that stretches the filament by alternating current applied.

The paper deals with some of already available nanotechnology-based methods for struggle against oncological diseases. We discuss the potentialities of essentially new approaches within which devices built inside diseased cells could operate their behaviour. Conceptually, using these approaches one can force such "controlled" cells to fight against tumours.

A method for direct experimental measurement of phases in X-ray diffraction analysis has been developed. The phases can be determined using a peculiar holographic filming (called here autoholography) in which the rays scattered on an object completely identical to the object under study but displaced, in a definite way, and turned in space relative to it serve as a reference beam. In principle, autoholography does not require any particularly good coherence of radiation since the reference bundle enables one to compensate to some extent for its absence. Therefore, X-rays used in X-ray diffraction analysis are well suited to autoholography.

The possibility of producing microparticles (10-1000 nm) suitable for the introduction into biological cells and tissues and producing the electrical field and electrical currents around them due to electrochemical and photoelectric processes is discussed. A number of phenomena related to antitumor immunity are discussed, and several hypotheses to explain them are invoked. Among them is the hypothesis that the antitumor activity of the immune system may be associated with some agents that are phagocytized by the cells of the macrophage series and promote their activation. Presumably, cell activation is triggered by the damage to phagosomes caused by the phagocytized agent. It is suggested to use for cell activation an artificial agent consisting of the above-mentioned electrically active microscopic particles. For example, it may consist of microscopic particles of semiconductor with zones of n- and p-type conductivity. Such particles act as microscopic photoelectric cells: when exposed to optical radiation, they generate a potential difference, which causes disruption and damage of phagosome membranes and results in the activation of immune cells.

A relatively simple means is proposed for fastening a macromolecule such as DNA in a straight line on a dielectric support (which is essential for "fast reading" of sequences by physical methods). A randomly coiled molecule in solution can be caused to align with a "straightening electrode" under the support, as in a phase transition. Conditions are envisaged that should ensure processive settling without defects.

The influence of imino acids on the thermodynamic characteristics of collagen type structures in various collagens has been analyzed. It was shown that the basic mechanism of entropy increase in the protein-water system consists in the alteration in the number of cooperative segments accompanying the increase in imino acids content, which can be observed during the melting of the fibrous macromolecule. The range of variation in the physical characteristics of cooperative units is determined, in particular, by the variability of hydrogen bond parameters. This is displayed in a broadening of the bands of NH-valence vibrations and the half-widths of transitions in post-denatured structures. Thus, the basic mechanism of the influence of imino acids on thermodynamic characteristics of collagens is related to the complex nature of the melting process. The dehydration-hydration mechanisms of native and denatured states become significantly different upon replacement of any amino acid by an imino acid.

A possible explanation for the occurrence of periodicity in the fine structure of histograms during nuclear decay is proposed. The hypothesis states that, even in the absence of polarization, when the spin distribution of decaying nuclei over directions is, on the average, isotropic, the fine structure of histograms should depend, due to fluctuations, on the angles at which the sample is observed. There fore, when the Earth after some period would make a full furn, the distribution of fluctuations would return to the initial one, and, correspondingly, the fine structure of the histograms would repeat.

The fundamental gnoseological question that is always present in a basic science is: Can this science adequately predict the future? In classical mechanics, we deal in many cases with dynamic chaos; therefore, this prediction is most often impossible. In the quantum theory, the dynamic chaos associated with the disturbances of initial conditions is formally absent. Nevertheless, as it was shown in this work, there are other reasons that directly relate to what is called the paradoxes of formal logic, which, in the case of quantum theory, too, do not enable one to precisely determine what will happen in the future.

The results of theoretical calculations of interactions between macromolecules dissolved in ordered media such as liquid crystals and biological membranes (lipid bilayers) are reviewed. Expressions for the potentials of interactions between macromolecules of different shape incorporated into nematic liquid crystals, thin films, and lipid mono- and bilayers were derived. In addition to exact expressions, simple evaluating formulae are given. The two-dimensional "gas" of macromolecules swimming on the membrane was considered, and the expression of state for this "gas" was derived. It was shown that in the "gas", phase transitions accompanied by the formation of two-dimensional clusters may occur. The estimates of critical density at which these transitions occur are given.

At present there is no generally accepted theory of the effect of macroscopic fluctuations. It the article, an attempt is made to relate this effect to some basic properties of quantum systems, in particular, to the formal absence of dynamic chaos in these systems. Based on this approach, it was shown why the level of the effect must be of the same order of magnitude as the level of noise and cannot exceed this level as the number of experiments increases. It was shown qualitatively what is the cause of the similarity of histograms observed in different experiments.

A new method of contact thermography (intrograph) was developed. The method allows one to establish the temperature in any region of the body. The computer program provides an uninvasive and safe way of comparison of thermograms in time. The obviously known biomedical parameters allow one to locate and characterize pathology foci. The accuracy of one temperature measurement is not worse than 0.01 deg at a measurement time of about one second.

Van der Waals interaction energy in globular proteins is presented by the interaction energies between regions of protein spatial structure with homogenous medium density distribution. We introduce a notion of the local medium permittivity as a function of absorptance of molecular groups with particular conformation. Proposed theory avoids shortcomings which are typical for the calculations on the basis of the pairwise additive approximation. The approach takes into account local peculiarities of protein spatial structure and physical-chemical characteristics of amino acid residues and molecular groups.

An algorithm for determining of protein domain structure is proposed. Domain structures resulted from the algorithm application have been obtained and compared with available data. The method is based on entirely physical model of van der Waals interactions that reflects as illustrated in this work the distribution of electron density. Various levels of hierarchy in the protein spatial structure are discerned by analysis of the energy interaction between structural units of different scales. Thus the level of energy hierarchy plays role of sole parameter, and the method obviates the use of complicated geometrical criteria with numerous fitting parameters. The algorithm readily and accurately locates domains formed by continuous segments of the protein chain as well as those comprising non-sequential segments, sets no limit to the number of segments in a domain. We have analyzed 309 protein structures. Among 277 structures for which our results could be compared with the domain definitions made in other works, 243 showed complete or partial coincidence, and only in 34 cases the domain structures proved substantially different. The domains delineated with our approach may coincide with reference definition at different levels of the globule hierarchy. Along with defining the domain structure, our approach allows one to consider the protein spatial structure in terms of the spatial distribution of the interaction energy in order to establish the correspondence between the hierarchy of energy distribution and the hierarchy of structural elements.

The problem in the calculation of Van der Waals interactions in protein globules based on the theory of condensed media was considered. The Van der Waals interactions are represented as energies of interaction of regions with a uniform density distribution. A definition of the local dielectric constant as a function of coefficients of absorption of molecular groups with a particular conformation was introduced. The applicability of this approach was estimated. The theory enables one to circumvent the problems arising in calculations based on pairwise additive approximation. The methods provides a high accuracy in determining the local features of spatial structures of globular proteins and physicochemical characteristics of their constituent amino acids and molecular groups.

The microscopic study of heat expansion of monoclinic pepsin crystals was performed in temperature interval of -120 degrees C to +20 degrees C. The coefficient of heat expansion along the C axis was shown to be 8-10 times as large as along the B axis. This dynamics anisotropy is interpreted to reflect the domain mobility of the molecule.

Liposomes bearing anti-fibronectin antibodies and associated with ferromagnetic particles bound firmly to the surface of mouse embryo fibroblasts. Upon binding magnetoliposomes, the cells could be sorted in a magnetic field.

Liposome-entrapped ferromagnetic particles are bound to the surface of L cells. A system of circular magnets is capable of concentrating magnetoliposome-bound cells, separating them from free cells. Antibodies associated with magnetoliposomes enable to concentrate selectively the target cells. Magnetoliposomes could be used for developing a new cell-sorting system.

Methods are proposed for determining values and positions of energetic barriers of monoionic channel according to its voltage clamp characteristics. In the cases when current fluctuation through the channels are conditioned by small deformations of its structure parameters of these deformations can be estimated by the autocovariational function of the current (or resistance).

Assuming a hypothesis on the existence of certain mathematical analogy between the work of the genetic apparatus of Metazoa cells and that of universal computer a number of predictions are advanced (which can be in principle tested experimentally) as to the functioning of this genetic apparatus. Presence of multicellular regions in DNA without semantic information in the form of proteins is explained; possible results of damage of these regions are predicted, existence of some objects moving along DNA and possessing a number of unusual properties as compared with the studied objects of this type is predicted.