Testing of the implicit membrane model
(read about implicit membrane model)
Hydrophobic segment (69–97) of human glycophorin A (GpA)
One of the most suitable objects for model testing is the hydrophobic segment of human glycophorin A (GpA). This peptide is relatively short (29 residues), which significantly simplifies treatment of the simulation results. Structure of this peptide had been determined via NMR spectroscopy in DPC micelles. And, finally, it forms dimers in the membrane environment, thus hereafter its investigation could be expanded on analysis of protein–protein interaction in membrane.
On the first step of simulations, calculation protocol, tested in the analysis of poly-Leu, was used. Low-energy structures had formed two structural groups: (1) transmembrane α-helix and (2) helical hairpin (see figure). Its conformational energies were closed, so proposed model could not range these states. Possible cause of such structural heterogeneity consists in symmetrical properties of implicit membrane. Natural cell membranes are strongly asymmetric by lipid composition, transmembrane electrostatic potential etc. To take into account this asymmetry membrane model has been elaborated by addition of term mimic influence of transmembrane electrostatic potential.
MC conformational search was prolonged with modified membrane model. As a result only native-like TM conformations were observed in low-energy structural set.
Fusogenic peptide of Influenza A hemagglutinin (HA) and its homologs
Correlation of simulations results and experimental data validates applicability of the membrane model to the analysis of interaction of helical peptides with the membrane. Thus, we can use this approach in study of the peptides with lack of experimental information. One of such type of objects is fusogenic peptides. The purpose of this investigation was delineation of features connected with fusogenic activity of the peptides.
HA and set of its analogs with and without fusogenic activity were analyzed on their mode of membrane binding and distribution of hydrophobic properties along the peptide.
Read about molecular hydrophobicity potential (MHP).
Address: 117997 Russia, Moscow, ul. Miklukho-Maklaya 16/10.