Isolated transmembrane helices arranged across a membrane: computational studies.

A computational procedure for predicting the arrangement of an isolated helical fragment across a membrane was developed. The procedure places the transmembrane helical segment into a model triple-phase system 'water-octanol-water'; pulls the segment through the membrane, varying its 'global' position as a rigid body; optimizes the intrahelical and solvation energies in each global position by 'local' coordinates (dihedral angles of side chains); and selects the lowest energy global position for the segment. The procedure was applied to 45 transmembrane helices from the photosynthetic reaction center from Rhodopseudomonas viridis, cytochrome c oxidase from Paracoccus denitrificans and bacteriorhodopsin. In two thirds of the helical fragments considered, the procedure has predicted the vertical shifts of the fragments across the membrane with an accuracy of -0.15 +/- 3.12 residues compared with the experimental data. The accuracy for the remaining 15 fragments was 2.17 +/- 3.07 residues, which is about half of a helix turn. The procedure predicts the actual membrane boundaries of transmembrane helical fragments with greater accuracy than existing statistical methods. At the same time, the procedure overestimates the tilt values for the helical fragments.

[Conformational-functional relationships of tetragastrin analogs]. / Konformatsionno-funktsional'nye otnosheniia analogov tetragastrina.

Sets of low-energy backbone conformations of the active tetragastrin analogue Boc-Trp-Leu-Asp-Phe-NH2 and two competitive antagonists Boc-Trp-Leu psi (CH2NH)-Asp-Phe-NH2 and Boc-Trp-Leu-Asp-O-CH2-CH2-C6H5 were obtained using theoretical conformational analysis methods. Groups of the conformations were selected for the three analogues, allowing a spatial matching of Trp, Asp and Phe residues responsible for the gastrin receptor binding. Three conformations possessing the lowest energies among the geometrically similar structures of these three peptides are suggested as a model for the "receptor-bound" conformations of these analogues. Backbone spatial folding resembling an alpha-helix turn is characteristic of these conformations. The correspondence of the proposed model to the available data on structure--activity relationships for tetragastrin analogues is discussed. Orientations of the putative receptor-bound conformations in a "water--lypophylic medium" two-phase system were investigated.

[Amphiphilic properties of angiotensin and its fragments]. / Amfifil'nye svoistva angiotenzina i ego fragmentov.

Many biologically active peptides are supposed to interact with specific receptors mainly due to hydrophobic forces. In order to obtain a more detailed information about the peptide molecule behavior at the "water-non-polar-phase" boundary an approach to the calculation of stable conformations on such a boundary has been developed. This approach is used for investigation of the amphiphilic properties of angiotensin and its six fragments. The results of calculations of transfer energies of these peptides from the water environment to the phase boundary are in agreement with the experimental data.

[Peptides of the "middle molecule" group]. / Peptidy gruppy "srednikh molekul".

The "middle molecules", endotoxins of peptide nature appearing in biological fluids in several diseases, cause the disorder of many regulatory processes, suppress the functions of blood cells, affect the transport characteristics of cell membranes. The review covers different aspects of formation, structure and numerous biological effects of "middle molecules", including the molecular mechanism of their biological action.