Monte Carlo on the manifold and MD refinement for binding pose prediction of protein-ligand complexes: 2017 D3R Grand Challenge.

Manifold representations of rotational/translational motion and conformational space of a ligand were previously shown to be effective for local energy optimization. In this paper we report the development of the Monte-Carlo energy minimization approach (MCM), which uses the same manifold representation. The approach was integrated into the docking pipeline developed for the current round of D3R experiment, and according to D3R assessment produced high accuracy poses for Cathepsin S ligands.

ClusPro FMFT-SAXS: Ultra-fast Filtering Using Small-Angle X-ray Scattering Data in Protein Docking.

We have recently demonstrated that incorporation of small-angle X-ray scattering (SAXS)-based filtering in our heavily used docking server ClusPro improves docking results. However, the filtering step is time consuming, since ≈10 conformations have to be sequentially processed. At the same time, we have demonstrated the possibility of ultra-fast systematic energy evaluation for all rigid body orientations of two proteins, by sampling using Fast Manifold Fourier Transform (FMFT), if energies are represented as a combination of convolution-like expressions.

Use of deep neural network ensembles to identify embryonic-fetal transition markers: repression of in embryonic and cancer cells.

Here we present the application of deep neural network (DNN) ensembles trained on transcriptomic data to identify the novel markers associated with the mammalian embryonic-fetal transition (EFT). Molecular markers of this process could provide important insights into regulatory mechanisms of normal development, epimorphic tissue regeneration and cancer. Subsequent analysis of the most significant genes behind the DNNs classifier on an independent dataset of adult-derived and human embryonic stem cell (hESC)-derived progenitor cell lines led to the identification of gene as a potential EFT marker.

Pepsi-SAXS: an adaptive method for rapid and accurate computation of small-angle X-ray scattering profiles.

A new method called Pepsi-SAXS is presented that calculates small-angle X-ray scattering profiles from atomistic models. The method is based on the multipole expansion scheme and is significantly faster compared with other tested methods. In particular, using the Nyquist-Shannon-Kotelnikov sampling theorem, the multipole expansion order is adapted to the size of the model and the resolution of the experimental data.

The cornucopia of meaningful leads: Applying deep adversarial autoencoders for new molecule development in oncology.

Recent advances in deep learning and specifically in generative adversarial networks have demonstrated surprising results in generating new images and videos upon request even using natural language as input. In this paper we present the first application of generative adversarial autoencoders (AAE) for generating novel molecular fingerprints with a defined set of parameters. We developed a 7-layer AAE architecture with the latent middle layer serving as a discriminator.

Protein-protein docking by fast generalized Fourier transforms on 5D rotational manifolds.

Energy evaluation using fast Fourier transforms (FFTs) enables sampling billions of putative complex structures and hence revolutionized rigid protein-protein docking. However, in current methods, efficient acceleration is achieved only in either the translational or the rotational subspace. Developing an efficient and accurate docking method that expands FFT-based sampling to five rotational coordinates is an extensively studied but still unsolved problem.

Main results of the 2012 joint Norwegian-Russian expedition to the dumping sites of the nuclear submarine K-27 and solid radioactive waste in Stepovogo Fjord, Novaya Zemlya.

This paper reports the main results of the 2012 joint Norwegian-Russian expedition to investigate the radioecological situation of the Stepovogo Fjord on the eastern coast of Novaya Zemlya, where the nuclear submarine K-27 and solid radioactive waste was dumped. Based on in situ gamma measurements and the analysis of seawater and sediment samples taken around the submarine, there was no indication of any leakage from the reactor units of K-27. With regard to the radioecological status of Stepovogo Fjord, activity concentrations of all radionuclides in seawater, sediment and biota in 2012 were in general lower than reported from the previous investigations in the 1990s.

Impact of distance-based metric learning on classification and visualization model performance and structure-activity landscapes.

This study concerns large margin nearest neighbors classifier and its multi-metric extension as the efficient approaches for metric learning which aimed to learn an appropriate distance/similarity function for considered case studies. In recent years, many studies in data mining and pattern recognition have demonstrated that a learned metric can significantly improve the performance in classification, clustering and retrieval tasks. The paper describes application of the metric learning approach to in silico assessment of chemical liabilities.

[Effect of total hypothermia on the fatty acid composition of blood phospholipids of rats and sousliks and light irradiation on chemical processes in lipid extract].

Effect of hypothermia on the fatty acid composition of rat and souslik blood phospholipids is studied. Different reaction of these animals to cooling is revealed: in rats no changes were observed in the fatty acid composition of blood phospholipids, whereas in the hibernating there were significant changes in the content of individual fatty acids (FA). The content of monoenic acids in sousliks decreased almost by 50%, while the content of saturated acid (C18) and of polyenic acids C18 : 2omega6 and C20 : 4omega6 rose significantly.

[Changes of gas exchange parameters and of functional-biochemical properties of erythrocytes in dynamics of experimental anemia in rats].

In experiments on Wistar male rats, on a specially constructed computer installation, O2 consumption by the animals in comparison with changes of hematological, biochemical, and rheological blood properties is studied after anemization--acute bloodletting (12-15% of the total blood mass). An increase of the O2 consumption by the organism and tissues by 18-28% has been revealed for the first 7 days after the bloodletting, in spite of a pronounced decrease of hematocrit, and of the amount of erythrocytes and hemoglobin in peripheral blood by 20-25% of the initial level. There was a 5-10-fold increase of the content of immature erythrocyte forms--reticulocytes and a progressive rise of cell acidic resistance, which is characteristic of young erythrocyte forms.

[Changes of physiological and biochemical characteristics of rat erythrocytes after blood loss].

In experiments of Wistar male rats, changes are studied of erythrocyte hematological, biochemical (activitities of transport ATPases), and rheological properties (capability for aggregation and deformability) 7 days after bloodletting of 12-15 % of the total blood mass. It has been shown that alongside with an elevation of erythrocyte volume and of the number of immature cells - reticulocytes, there was a statistically significant increase of Na,K-ATPase and Ca-ATPase activities in the whole erythrocytes and their membrane preparations - ghosts, the increment of activity in the case of Na,K-ATPase being essentially higher in the whole cells. This indicates the appearance of an enzyme activator inside the erythrocytes.

Direct methods for radionuclides measurement in water environment.

The paper is devoted to the direct method of anthropogenic radionuclide measurement in the water environment. Opportunities of application of submersible gamma-spectrometers for in situ underwater measurements of gamma-radiating nuclides and also the direct method for 90Sr detection are considered.

Rheologic properties of mammalian erythrocytes: relationship to transport ATPases.

Rheologic properties of erythrocytes and activities of their Ca(2+)-ATPase and Na+, K(+)-ATPase were analyzed together with standard erythrocyte values in seven mammalian species (man, rat, mouse, rabbit, hamster, guinea pig and dog). The number of erythrocytes in the blood of animals investigated correlated inversely with the mean cell volume (MCV) (r = -0.936, P = 0.

Species variability of erythrocyte transport ATPases in mammals.

Na+, K(+)-ATPase, and Ca(2+)-ATPase in whole erythrocytes from five species of mammals (rat, mouse, guinea pig, golden hamster, rabbit) after cell treatment with Tween 20 (7.5 mg/ml) varied over a wide range: from 3.0 +/- 0.

[A comparative study of the properties of ouabain-sensitive phosphatase in rat erythrocyte ghosts and spectrin-free membranes].

The removal of the membrane skeleton proteins (MSP), chiefly spectrin and actin, from the rat erythrocyte ghosts was shown to result in a decrease of both the total Na, K-ATPase activity and a partial reaction of the enzyme, namely the phosphatasic one. Besides, modulating effects of the effectors promoting the enzyme conformational transitions (ATP and Mg2+) on the ouabain-sensitive K-phosphatase is changed. For instance, a pronounced activation of the K-phosphate in a high-potassium medium in the presence of 1 mM ATP disappeared and the degree of the enzymatic activity enhancement in response to increasing MgCl2 concentrations (from 1.

[The effect of hemolysate and calcium ions on transport ATPase activity in guinea pig erythrocytes].

Influence of 0.1, 0.3 and 1.

[A comparative study of the intracellular regulation of transport ATPase activity in non-nucleated erythrocytes].

Removing the basic cytoskeleton proteins (spectrin, 4.1 and 2.1 band proteins) from the unnuclear erythrocyte membranes of four mammalian species (mouse, hamster, guinea, pig and rabbit) made no changes in Na,K-ATPases, while the specific activity of Ca-ATPases was decreased (the decreasing was of a range of 60-90% depending on the species, in values per mg of protein).

[The activity of transport ATPases and the characteristics of the protein-lipid composition of the membranes of anuclear erythrocytes in a number of mammals].

The activity of Na,K-ATPase and Ca-ATPase of the intact erythrocytes and their membrane preparations and also fatty acid, phospholipid and protein content of erythrocyte membrane of guinea pig, mouse, rabbit and hamster have been examined. The activity of Na,K- and Ca-ATPase in intact erythrocytes varies significantly among different species while the level of activity of these enzymes in their membrane preparations differs slightly. Together with the results of investigations of chemical composition of the erythrocyte membrane of these species which show the principal homogeneity of their fatty acid, phospholipid and protein composition, these data indicate the existence of the system of intracellular modulators, that maintain the activity of these enzymes on the species specific level.

[Na, K-ATPase activity in the erythrocyte membrane preparations and kidneys of spontaneously hypertensive rats].

The enzyme activity in the cortex and medulla of the SHR was 1.5-2.0-fold lower than that of the WKY and Wistar rats.

[The activity and properties of K-pNPphosphatase in membrane preparations of erythrocytes with different polypeptide compositions in Wistar, Wistar-Kyoto and SHR strain rats].

A higher K-pNPPase activity was found in erythrocyte membrane preparations from the SHR as compared with the Wistar rats. Removal of peripheral proteins from the membrane skeleton depressed the K-phosphatase activity and eliminated the difference between the SHR and Wistar rats. No activating effect of the ATP and Ca on the enzyme was found.