Toll-like receptor 3 transmembrane domain is able to perform various homotypic interactions: An NMR structural study

AbstractToll-like receptors (TLRs) take part in both the innate and adaptive immune systems. The role of the transmembrane domain in TLR signaling is still elusive, while its importance for the TLR activation was clearly demonstrated. In the present study the ability of the TLR3 transmembrane domain to form dimers and trimers in detergent micelles was shown by solution NMR spectroscopy. Spatial structures and free energy magnitudes were determined for the TLR3 transmembrane domain in dimeric and trimeric states, and two possible surfaces that may be used for the helix–helix interaction by the full-length TLR3 were revealed

A Solvent Model for Simulations of Peptides in Bilayers. I. Membrane-Promoting α-Helix Formation

AbstractWe describe an efficient solvation model for proteins. In this model atomic solvation parameters imitating the hydrocarbon core of a membrane, water, and weak polar solvent (octanol) were developed. An optimal number of solvation parameters was chosen based on analysis of atomic hydrophobicities and fitting experimental free energies of gas-cyclohexane, gas-water, and octanol-water transfer for amino acids. The solvation energy term incorporated into the ECEPP/2 potential energy function was tested in Monte Carlo simulations of a number of small peptides with known energies of bilayer-water and octanol-water transfer. The calculated properties were shown to agree reasonably well with the experimental data. Furthermore, the solvation model was used to assess membrane-promoting α-helix formation. To accomplish this, all-atom models of 20-residue homopolypeptides—poly-Leu, poly-Val, poly-Ile, and poly-Gly in initial random coil conformation—were subjected to nonrestrained Monte Carlo conformational search in vacuo and with the solvation terms mimicking the water and hydrophobic parts of the bilayer. All the peptides demonstrated their largest helix-forming tendencies in a nonpolar environment, where the lowest-energy conformers of poly-Leu, Val, Ile revealed 100, 95, and 80% of α-helical content, respectively. Energetic and conformational properties of Gly in all environments were shown to be different from those observed for residues with hydrophobic side chains. Applications of the solvation model to simulations of peptides and proteins in the presence of membrane, along with limitations of the approach, are discussed

A Solvent Model for Simulations of Peptides in Bilayers. II. Membrane-Spanning α-Helices

AbstractWe describe application of the implicit solvation model (see the first paper of this series), to Monte Carlo simulations of several peptides in bilayer- and water-mimetic environments, and in vacuum. The membrane-bound peptides chosen were transmembrane segments A and B of bacteriorhodopsin, the hydrophobic segment of surfactant lipoprotein, and magainin2. Their conformations in membrane-like media are known from the experiments. Also, molecular dynamics study of surfactant lipoprotein with different explicit solvents has been reported (Kovacs, H., A. E. Mark, J. Johansson, and W. F. van Gunsteren. 1995. J. Mol. Biol. 247:808–822). The principal goal of this work is to compare the results obtained in the framework of our solvation model with available experimental and computational data. The findings could be summarized as follows: 1) structural and energetic properties of studied molecules strongly depend on the solvent; membrane-mimetic media significantly promote formation of α-helices capable of traversing the bilayer, whereas a polar environment destabilizes α-helical conformation via reduction of solvent-exposed surface area and packing; 2) the structures calculated in a membrane-like environment agree with the experimental ones; 3) noticeable differences in conformation of surfactant lipoprotein assessed via Monte Carlo simulation with implicit solvent (this work) and molecular dynamics in explicit solvent were observed; 4) in vacuo simulations do not correctly reproduce protein-membrane interactions, and hence should be avoided in modeling membrane proteins

Спосіб стиснення парорідинного середовища

Спосіб стиснення парорідинного середовища включає подання активного середовища в активне сопло, створення робочого потоку насиченої пари, ежектування робочим потоком насиченої пари в камеру змішування пасивної парорідинної суміші, стиснення суміші середовищ на виході з камери змішування і відокремлення зі стисненого парорідинного середовища рециркуляційної насиченої при тиску стиснення рідини в сепараторі та відкачування її з конденсатовідвідника.Способ сжатия парожидкостной среды включает подачу активной среды в активное сопло, создание рабочего потока насыщенного пара, эжектирование рабочим потоком насыщенного пара в камеру смешения пассивной парожидкостной смеси, сжатие смеси среды на выходе из камеры смешения и отделение из сжатой парожидкостной среды рециркуляционной насыщенной при давлении сжатия жидкости в сепараторе и откачку ее из конденсатоотводчика.A method of compression of a steam-liquid medium includes supply of the active medium in an active nozzle, creating a workflow of saturated steam, ejection by a working medium of saturated steam into in a mixing chamber of passive steam-liquid mixture, compression of the fluid mixture at the outlet from the mixing chamber and separation from the compressed steam-liquid medium of recirculation liquid saturated at a pressure of compression in the separator and its pumping from the condensate drain