[Prediction of Protein Conformational Mobility and Evaluation of Its Reliability Using Small-Angle X-ray Scattering].

The "coarse-grained" model of protein conformational mobility is presented. We compared the trajectories of conformational motions predicted for five proteins using this model with the motion obtained by the method of the "nearest neighbor", based on small-angle X-ray scattering data. It is shown that for all studied proteins the sequence of conformations calculated on the basis of "coarse-grained" model and on the basis of the "nearest neighbor", coincides well, although there are exceptions. Some separate consideration should be given to each protein to discern the causes of these exceptions.

[The "block" approach in x-ray diffusion dispersion as a method of studying the packing of secondary structure elements in globular proteins]. / "Blochnyi" podkhod v rentgenovskom diffuznom rasseianii kak metod issledovaniia upakovki élementov vtorichnoi struktury v globuliarnykh belkakh.

To calculate large angle scattering intensity of biopolymers in solution a "block" method of modeling the globular proteins structures is suggested: conformation of protein alpha-helical and beta-structural parts are described in detail, whereas the remaining part of the macromolecule is substituted by a continuum with homogeneous electron density. A comparison of large-angle scattering curves on the basis of the "block" method and the exact structure was made for a number of alpha-helical and beta-structural globular proteins. It is shown that there is a qualitative agreement between the "exact" and model curves.

[Rotation isomerization of side chains of globular proteins and its effect on the x-ray scattering curves of proteins in a solution]. / Povorotnaia izomerizatsiia bokovykh grupp globuliarnykh belkov i ee vliianie na indikatrisu rentgenovskogo rasseianiia belkov v rastvore.

A new method has been developed for averaging the intensity of X-ray diffuse scattering of proteins by different conformations of side groups. The method is based on the algorithm allowing to calculate statistical weights of rotation isomers of side chains. It is shown that for protein structures obtained from high resolution crystallographic data, conformations of the majority of surface groups correspond to rotation isomers with the greatest statistical weight. It has been found that for medium size proteins (with molecular weight varying from 15,000 to 30,000 dalton) whose structure has been determined at high resolution, the influence of rotation isomerization of side chains on the scattering indicatrices does not exceed 5%. The influence of side chains mobility on the scattering curves of large proteins is also small. For these two classes of proteins the rotation isomerization of side groups can be ignored when interpreting significant (exceeding 10%) divergences between experimental and theoretical scattering curves.

[Calculation of x-ray diffuse scattering curves for DNA A- and B-forms in solution]. / Raschet indikatris rentgenovskogo diffuznogo rasseianiia A- i B-form DNK v rastvore.

To obtain strictest theoretical indicatrices of X-ray scattering as well as to determine the volume and surface of DNA A- and B-forms in solution a new "cube" method has been applied which has been developed earlier for description of scattering intensity and geometric characteristics of particles with a complex surface topography. A new approach to calculation of diffuse scattering intensity of strongly elongated particles in solution has been proposed. Hydration of DNA molecules has been shown to considerably affect their X-ray scattering indicatrices. It has been also shown that the known Langridge method satisfactorily describes the DNA scattering indicatrix in the large-angle region but cannot be applied to analysis of DNA scattering intensity in the small-angle and large-angle ranges of the scattering curve simultaneously.

[Calculation of the surface and volume of proteins in solution]. / Metod rascheta poverkhnosti i ob"ema belka v rastvoritele.

The volume occupied by the particle in the solvent and also its molecular and accessible surfaces were described with a system of small cubes (the edge length approximately 0.3 A). We have compared the ratios between molecular and accessible surface areas for a number of proteins, and different extent of jaggedness of the molecular surface of these proteins was revealed. For the studied proteins the volume occupied by the protein in the solvent calculated by this technique is close to that estimated from the experimental partial specific protein volume.

[Analysis of fractal properties of globular protein surfaces by means of small-angle x-ray scattering]. / Analiz fraktal'nykh svoistv poverkhnostei globuliarnykh belkov metodom rentgenovskogo diffuznogo rasseianiia.

The "cube method" [M. Yu. Pavlov, B. A. Fedorov, Biopolymers, 22, 1507, 1983] has been used to calculate the intensity of the large-angle X-ray scattering from the volumes of several globular proteins. In the logarithmic plots of the scattered intensity curves from three of these proteins, there is a linear region at scattering angles corresponding to Bragg distances of from about 6.3 A to 21 A. This linear region possibly may be due to the fractal properties of the surfaces of these proteins on length scoles from 6.3 A to 21 A, and the fractal dimensions corresponding to the power-law scattering at these scattering angles have been evaluated.

[Possibility of wide-angle neutron scattering in the study of proteins and nucleic acids in solutions]. / Vozmozhnosti bol'sheuglovogo neitronnogo rasseianiia pri issledovanii belkov i nukleinovykh kislot v rastvore.

A method is proposed for calculating wide-angle neutron scattering curves of biopolymers at any fraction of heavy water (D2O) in solution. The method permits to accurately take into account the phenomenon of deuteroexchange. By this method neutron scattering curves of proteins and DNA have been calculated. The calculations have shown that at optimal fractions of D2O in solution the profiles of neutron scattering curves and their sensitivity to conformational rearrangements in protein molecules turned out to differ very little from those of corresponding X-ray curves. Thus the neutron scattering curves do not contain any additional information (as compared with those contained in X-ray scattering curves) on the structure of proteins in solution. On the contrary, neutron and X-ray scattering curves of DNA differ significantly at all fractions of D2O in solution and therefore the methods of wide-angle neutron and X-ray scattering could become mutually complementary in studying the structure of nucleic acids in solution.

[The effect of fixed water molecules on fractal properties of globular protein surfaces]. / Vliianie fiksirovannykh molekul body na fraktal'nye svoistva poverkhnostei globuliarnykh belkov.

On the base of the technique developed by the authors together with Schmidt the fractal properties of the 17 globular proteins have been analysed using the crystal structure data at high resolution. For all the proteins there are the coordinates of fixed water molecules in the protein data bank. For each protein the fractal dimension of its surface D has been calculated with and without taking into account the fixed water molecules located inside a 3-Angstrom hydrated layer. Small but systematic decrease of the DS values for the proteins with the fixed water molecules has been demonstrated. It means that the fixed water molecules tend to fill gaps on the protein surfaces and in that way to smooth the surfaces. The volumes and the molecular surfaces of the proteins have been also calculated on the base of the cube technique. The molecular surfaces of the proteins with the fixed water molecules prove to decrease. This fact can be considered as the indirect evidence that the protein surfaces become to be smoother.

[Wide-angle x-ray scattering comparison of the structure of crystalline cytochrome c and cytochrome c in solution]. / Sravnenie struktury tsi tokhroma c v kristalle i rastvore metodom rasseianiia rentgenovskikh luchei pod bol'shimi uglama.

Large-angle X-ray diffuse scattering has been used for studying the conformational changes in cytochrome c during its transition from crystal into solution and during a change of the electron state of the heme. It has been found that the structure of cytochrome c in solution differs from its structure in crystal by a shift of the chain fragment in the region of 60-77 amino acid residues. The studies of the oxidized, reduced and cyanoforms of protein in solution have not revealed noticeable changes in the protein structure.

[Comparison of the structures of different forms of sperm whale myoglobin in solution using wide angle x-ray scattering]. / Sravnenie struktur razlichnykh form mioglobina kashalota v rastvore s pomoshch'iu rentgenovskogo rasseianiia pod bol'shimi uglami.

Experimental X-ray diffuse scattering curves in a wide range of angles for oxy-, deoxy-, met- and cyan-forms of sperm whale myoglobin in solution have been obtained. It has been found that scattering indicatrices of these ligand forms of myoglobin are well compatible with each other and differ from the theoretical scattering curve of met-myoglobin, calculated from the structure of this protein in crystal. The conclusions have been drawn: (1) on the similarity of myoglobin structures in solution for all the protein forms studied; (2) on the difference in the structure of the above ligand forms of myoglobin in solution from the structure of the protein in crystal by a slight shift (about 2 A) of the "hairpin" GH.

[Diagnosis of dysfunctions of heart valve bioprostheses]. / Diagnostika disfunktsii bioprotezov klapanov serdtsa.

Twenty-three cases of bioprosthetic dysfunction due to infectious endocarditis and primary tissue degeneration are reviewed. Twelve bioprostheses were studied morphologically. Follow-up of bioprosthesis-wearers for timely diagnosis of bioprosthetic dysfunction can be based on routine clinical investigation procedures. Echocardiographic detection of calcified vegetations on the cusps, as well as thrombosis, incompetence and marked stenosis of the bioprosthesis are indications for repeated surgery.

[Dynamics of the phonocardiographic picture following the bioprosthesis of the mitral valve]. / Dinamika fonokardiograficheskoi kartiny posle bioprotezirovaniia mitral'nogo klapana serdtsa.

Patterns of phonocardiographic changes were studied in 67 patients (aged 20 to 51 years) with acquired mitral disease 2 months to 6 years after the implantation of aortic xenobioprostheses, preserved in glutaraldehyde and mounted on a hard or flexible support. Phonocardiographic findings were compared with intracardiac hemodynamic data. Three stages and three types of phonocardiographic pattern were identified in patients with normally functioning xenobiovalves. As the postoperative period grew longer, the patients showed progressively smaller amplitudes of tones I and II, a smaller, if any, systolic output murmur and diastolic murmur; some patients no longer exhibited the prosthetic opening tone. PCG parameters showed stability between 2 and 6 years of follow-up.

Diffuse scattering of x rays by polypeptides and proteins in solution. III. Analysis of scattering curve of sperm whale myoglobin.

X-ray scattering curves for the sperm whale myoglobin molecule and a model which includes only the helical regions of the polypeptide chain are calculated. The portion of the scattering curve associated with the packing of the helices inside the protein globule is analyzed. The model of the myoglobin molecule is used to investigate the sensitivity of the scattering curve to changes in the mutual packing of the helical regions.