[Atomic force field FFsol for calculation of molecular interactions of in water environment].

Detailed calculations of protein interactions with explicitly considered water takes enormous computer time. The calculation becomes faster if water is considered implicitly (as a continuous media rather than as molecules); however, these calculations are much less precise, unless one uses an additional (and also volumes) computation of the solvent-accessible areas of protein atoms. The aim of our study was to obtain parameters for non-bonded atom-atom interactions for the case when water surrounding is considered implicitly and the solvent-accessible areas are not computed.

[Protein structure prediction from analogy. III. Optimization of a combination of substitution matrices and pseudo-potentials used to align protein].

We describe a general and fast method of maximization of a "recognition ability" of a linear combination of an arbitrary number of various methods used to recognize protein structures and produce the sequence-to-structure alignments. It is shown that, at a low level of sequence similarity, the optimal combined method has a significantly higher "recognition ability" than each of participating separate method, the leading role in this combination being played by (1) pseudo-potentials of long-range interactions; (2) matrices of secondary structure similarity; and, finally, (3) amino acid substitution matrices. As to a high level of sequence similarity, here the leading and virtually the sole role in the optimal combination is played by substitution matrices, although admixture of pseudo-potentials of long-range interactions and matrices of secondary structure similarity somewhat increases the "recognition ability" of the combined method.

[Protein structure prediction from analogy. I. New database of spatially similar and dissimilar structures of protein domains for testing and optimization of prediction methods].

The paper describes creation and analysis of a database 3Dfold_test. This database consists of a large set of pairs of spatially-similar structures of protein domains and of an accompanying, much larger control set of "decoys", i.e.

[On the role of some conserved and nonconserved amino acid residues in transition state and in intermediate of apomyoglobin folding].

The effect of some amino acid residues in A, B, G, and H helices on the folding nucleus and folding intermediate state formation was estimated. For four apomyoglobin mutant forms with point replacements of hydrophobic amino acid residues by Ala, the influence of the substitutions on the stability of native (N) protein and its folding intermediate state (I) was studied, as well as on the protein folding/unfolding rates. Equilibrium and kinetic studies on mutant proteins over a wide range of urea concentrations have shown that the protein native state was strongly destabilized in comparison with that of the wild type protein.

[On prediction of folding nuclei in globular proteins].

The approach described in this paper on the prediction of folding nuclei in globular proteins with known three dimensional structures is based on a search of the lowest saddle points through the barrier separating the unfolded state from the native structure on the free-energy landscape of protein chain. This search is performed by a dynamic programming method. Comparison of theoretical results with experimental data on the folding nuclei of two dozen of proteins shows that our model provides good phi value predictions for proteins whose structures have been determined by X-ray analysis, with a less limited success for proteins whose structures have been determined by NMR techniques only.

[Kinetics of folding nuclei formation in proteins].

When a protein folds or unfolds, it passes through many half-folded microstates. Only a few of them can accumulate and be seen experimentally, and this happens only when the folding (or unfolding) occurs far from the point of thermodynamic equilibrium between the native and denatured states. The universal features of folding, though, are observed in the vicinity of the equilibrium point.

[When and how can homologs overcome errors in the energy estimates and make the 3D structure prediction possible].

One still cannot predict the 3D fold of a protein from its amino acid sequence, mainly because of errors in the energy estimates underlying the prediction. However, a recently developed theory [1] shows that having a set of homologs (i.e.

[Estimation of quality of approximation of atom-atom contacts of amino acid residues in proteins by the contacts of the residue force centers].

How precisely the atom-atom contacts of amino acid residues in proteins can be approximated by the contacts of amino acid residue "force centers"? To answer this question, we examined the force centers positioned in the C alpha-atom, the C beta-atom, in the optimal point of the C alpha-C beta axis, and in the geometrical center of residues. The maximal coefficient of correlation between the residue force center contacts and the presence of atom-atom contacts of the residues (85%) was obtained for the force centers positioned in geometrical centers of the residues. The correlation is 80% for the optimal position of the centers on the C alpha-C beta axes; a somewhat smaller value (78%) is obtained for the force centers positioned in C beta-atoms, and 71% only for the centers positioned in C alpha-atoms.

[Attainment of an energy minimum by a protein chain does not require a complete sorting of conformations: a computerized experiment and phenomenological theory].

We investigate how a protein chain achieves the lowest energy state by Monte Carlo simulation using a simple beta-sheet protein model. We show the existence of an optimal temperature range where the energy minimum is found quickly without any exhaustive sorting of the chain conformations even for random sequences. This optimal temperature range is determined by the critical temperature characteristic for the onset of freezing-out of a few lowest-energy chain folds.

[A rapid and precise method for lattice approximation of the course of a protein chain based on a dynamic programming algorithm].

Application of a dynamic programming method allows one to find the best possible lattice model of a protein chain fold for any lattice and any orientation of the protein relative to the lattice. Special repulsive potentials help to obtain the self-avoiding lattice models of protein folds. The quality of approximation increases when the distance between neighbor chain links is not fixed rigidly.

[De novo proteins with a given spatial structure: new approaches to design and analysis].

Based on the molecular theory of protein structure the de novo protein was designed in order to obtain the tertiary fold which has not yet been observed in natural proteins, namely four-stranded antiparallel beta-sheet covered by two alpha-helixes. The gene coding for this protein (named albebetin) was chemically synthesized, cloned in plasmid with SP6 phage promoter and expressed in mRNA-dependent cell-free translation system. An approach was developed to study albebetin using only nanogram amounts of radio labelled protein without previous purification.

[Determination of the folding of globular protein chain by the self-consistent field method].

It is shown that and how it is possible to single out the chain fold which is thermo-dynamically most stable. The suggested approach is based on two physical ideas: A "molecular field" approximation permits to examine all protein structures which belong to the same "folding pattern". Only a limited set of the "potentially stable" folding patterns have to be examined.

[Radionuclide assessment of microcirculatory disorders in varicose disease of the lower extremities].

Comprehensive assessment of macro- and microhemodynamics of the lower limbs in 61 patients with varicosis using radionuclide angiography and the method of 99m-Tc-pertechnetate clearance from the intracutaneous depot has shown that peripheral circulatory disturbances correspond to a stage of disease and trophic skin lesions depend on the state of microcirculation. Two types of microcirculatory disturbances have been revealed using a detailed analysis of indices of the blood circulation at the stage of decompensation: I--marked retardation of the capillary blood flow; II--the presence of arteriolovenular shunting. Radionuclide methods make it possible to unravel some problems related to the pathogenesis of disease and to obtain additional diagnostic information on radiopaque and ultrasonic investigations.

[Predicting the three-dimensional structure of alpha- and beta-interferons].

Secondary structures of leukocyte alpha 1- and alpha 2-interferons and of fibroblast beta-interferon are calculated using the molecular theory of protein secondary structures. The common secondary structure calculated for alpha- and beta-interferons is used to predict the three-dimensional structures of fragments 1-110 and 111-166 of the chains (which are supposed to be quasi-independent domains). The predicted structure of the active domain I (1-110) is an "up-and-down" tetrahelical complex (in which the second helix is shorter than the others and can be missed in alpha 1-interferon) similar to the mirror-image of myohaemoerythrin.

[Fluctuating state of the protein globule].

It has been shown that bovine and human alpha-lactalbumins and carbonic anhydrase B can be transformed under different influence into a peculiar state possessing physical characteristics intermediate between those for the native and unfolded states. In this state a protein molecule is compact and has the secondary structure similar to that of the native molecule, but does not melt cooperatively at heating, has an anomalously fast H-D exchange and a more or less symmetrical average environment of aromatic and other side groups. A model of this "intermediate" state of protein molecule is proposed, according to which the intermediate state differs from the native one mainly by the substantial increase of protein structure fluctuations and the sharp decrease of van der Waals and other specific interactions.

[Protein globule without the unique three-dimensional structure: experimental data for alpha-lactalbumins and general model].

It has been shown that bovine and human alpha-lactalbumins under the influence of acidic pH, high temperatures or low guanidine hydrochloride concentrations are transferred into a state which is quite distinct both from the native and the completely denatured (unfolded) ones. Human alpha-lactalbumin can be transferred into this intermediate state also by removal of the bound to it Ca2+ ion. On the basis of the obtained physical characteristics of this state a model of the "intermediate" state is suggested in which a protein globule is compact, has a secondary structure, but does not possess a unique three-dimensional structure.