Protein-protein docking predictions for the CAPRI experiment

We predicted structures for all seven targets in the CAPRI experiment using a new method in development at the time of the challenge. The technique includes a low-resolution rigid body Monte Carlo search followed by high-resolution refinement with side-chain conformational changes and rigid body minimization. Decoys (approximately 10(6) per target) were discriminated using a scoring function including van der Waals and solvation interactions, hydrogen bonding, residue-residue pair statistics, and rotamer probabilities. Decoys were ranked, clustered, manually inspected, and selected. The top ranked model for target 6 predicted the experimental structure to 1.5 A RMSD and included 48 of 65 correct residue-residue contacts. Target 7 was predicted at 5.3 A RMSD with 22 of 37 correct residue-residue contacts using a homology model from a known complex structure. Using a preliminary version of the protocol in round 1, target 1 was predicted within 8.8 A although few contacts were correct. For targets 2 and 3, the interface locations and a small fraction of the contacts were correctly identified.     

A chemosensory gene family encoding candidate gustatory and olfactory receptors in Drosophila

A novel family of candidate gustatory receptors (GRs) was recently identified in searches of the Drosophila genome. We have performed in situ hybridization and transgene experiments that reveal expression of these genes in both gustatory and olfactory neurons in adult flies and larvae. This gene family is likely to encode both odorant and taste receptors. We have visualized the projections of chemosensory neurons in the larval brain and observe that neurons expressing different GRs project to discrete loci in the antennal lobe and subesophageal ganglion. These data provide insight into the diversity of chemosensory recognition and an initial view of the representation of gustatory information in the fly brain.     

Molecular basis of the biological activity of substances and homeopathic remedies at zero concentrations

While getting ultra los dosages in serial dilutions interactions between a substance and impurities of a solvent occur parallel with diminishing of concentrations. The concentration of impurities in high dilutions prevails the calculated concentration of substrate. Experiments show that different concentrations of compounds of impurities in a solvent correspond to different substances in different dilutions, including < 10(-24) mol/l. While dissolving three components--a solvent, impurities and a substance--participate in two processes: changing of concentration and changing of composition. Changed chemical composition of impurities of a solvent reflects specificity of physicochemical properties of a dissolving substance and is the molecular basis for biological activity of solutions with a concentration lower than 10(-24) mol/l.     

Mutation in the structure of exon 7 of the phenylalanine hydroxylase in phenylketonuria patients from the Novosibirsk area

The spectrum and frequency of mutations of exon 7 of the gene for phenylalanine hydroxylase (PAH) were studied in 34 phenylketonuria (PKU) patients living in Novosibirsk oblast. The five most prevalent mutations constituted 17.64% of defective alleles: R243Q (1.47%), R252W (1.47%), R261Q (5.88%), E280K (1.47%), and P281L (7.35%). A neutral polymorphic locus V245V was found within exon 7.     

New polymorphic sites in the structure of the human phenylalanine hydroxylase gene

A previously unknown sequence of the human phenylalanine hydroxylase (PAH) gene intron 7 (GeneBank AN AF204239) has been reported. Screening of the group of phenylketonuria patients from Nobosibirsk region for polymorphic sites within intron 7 revealed single nucleotide substitutions at intron positions 332, 451, 574 and 791. Polymorphic site at intron position 791 corresponds to one of the eight restriction sites (MspI) utilized for haplotype construction. Analysis of the MspI allele frequencies in 29 phenylketonuria patients showed that the frequency of the MspI+ allele in this group was 79.4%. Polymorphic sites at nucleotide position +97 from the beginning of intron 10, and at nucleotide position -54 from the end of intron 5, were also described. The polymorphic sites revealed can be used as markers for identification of the PAH alleles in population genetic studies, and also serve for diagnostics of phenylketonuria (PKU). The presence of numerous nucleotide substitutions within the intronic sequences confirms highly polymorphic structure of the PAH gene.     

Blocking of cold paralysis of physiological functions

For more than 100-year history of studying hypothermia a rewarming of a cooled organism was always considered as the only method of restoring the cold-paralysed physiological functions and the vital activity of an overcooled organism of homoiothermal animals and humans. The paper gives the results of applying the method developed at our Laboratory, of restoring the cold-paralysed important physiological functions after a continuous cooling of rats, without rewarming the animals.     

A new micromethod for mechano-chemical research.

A new micromethod to study activity of enzymes in crystalline and amorphous solid samples subjected to tension is described. Both static (up to 200%) and dynamic (with an amplitude up to 50% and frequency of 10(-3)-50 Hz) deformation may be applied to the sample during the activity measurement. Strain-induced changes in activity of thin (3-10 microns) needle-like strips (0.2-0.5 microns long), cut out of the microtome sections of cross-linked crystals of pancreatic carboxypeptidase A is measured in a droplet of substrate solution (with volume of 10(-6)-10(-9) l) with a pH-microelectrode technique.     

Osmotic homeostasis as one of critical targets of cell damage by some environment factors

The analysis of ours and literary data confirmed author new conception of cell damage mechanism by some environment factors according which the system of osmotic homeostasis is one of the critical targets of such damage, is presented.