Molecules of the peptide H-(RADA)₄-OH in aqueous salt solutions are able of forming bilayer fibrils in the form of a biotropic material, which is suitable as a substrate for the growth and differentiation of vertebrate cells. In the filament, two β-sheets interact with hydrophobic surfaces formed by methyl groups of alanine residues. The charged groups of arginine and aspartic acid residues are exposed to the outside, while the peptides which make up the filament are in the β-conformation. Fibrils have two external hydrophilic layers, while a hydrophobic one is situated in between of them. Biogels from the H-(RADA)₄-OH peptide are considered as a prominent structure to design extracellular media aimed to culture different types of cells. Little is known about the detailed filament structure and peptide chain composition in two β-sheets. We have designed and studied the molecular dynamics of bilayered protofilament structures, whose β-sheets are composed either of parallel or antiparallel peptide chains. The method of molecular dynamics was used to study H-(RADA)₄-OH peptide complexes at 80 and 300 K. While the most stable peptide complex was found to consisting of antiparallel peptides, had the lowest free energy and the least deviation of atom coordinates, yet another stable structure of the peptide complex was identified as a 24-mer complex of parallel peptides with two β-sheets placed in syn orientation. These results further underlined the importance of factors which direct the initial stages of the H-(RADA)₄-OH self-assembling in solution.

A short synthetic peptide from the C-terminal part of the caveolin-3 structure was tested for experimental autoimmune encephalomyelitis (EAE) treatment in rats. The structure–function similarity established between the novel synthetic peptide of pCav3 and the well-known immunomodulator immunocortin determined pCav3’s ability to reduce EAE symptoms in Dark Agouti (DA) rats injected with pCav3 (500 µg/kg). pCav3 was found to interfere with the proliferation of lymphocytes extracted from the LNs of DA rats primed with homogenate injection, with IC₅₀ = 0.42 μM (2.35 mcg/mL). pCav3 affected EAE in a very similar manner as immunocortin. The high degree of homology between the amino acid sequences of pCav3 and immunocortin corresponded well with the therapeutic activities of both peptides, as demonstrated on EAE. The latter peptide, possessing a homologous structure to pCav3, was also tested on EAE to explore whether there were structural restrictions between these peptides implied by the MHC-involved cell machinery. Consequently, immunocortin was further examined with a different autoimmune disease model, collagen-induced arthritis (CIA), established in Sprague–Dawley rats. CIA was established using an intentionally different genetic platform than EAE. Based on the results, it was concluded that the effectiveness of pCav3 and immunocortin peptides in EAE rat model was almost identical, but differed in the rat model of rheumatoid arthritis; thus, efficacy may be sensitive to the MHC type of animals used to establish the autoimmune disease model.

Dynamics of 24 Self-Assembling H-(RADA) 4 -OH Peptides Complexed in Bi-Layered Structure with Layers in syn and anti Orientation Oсoбeннoсти кoмплeксoв самоорганизующихся пeптидoв H-(RADA) 4 -OH со слoями в syn - и anti -ориентации

The theory of fluids is used to modify the integral equations of the reference interaction site model (RISM) approximation. Its applicability to the study of biomolecules solvation is evaluated. Unlike traditional RISM applications, the new integral equation contains an intramolecular correlation matrix that only needs to be calculated once. This allows us to bypass the effort of repeatedly solving RISM equations and the time-consuming averaging of values obtained for each time point of a molecular trajectory. The new approach allows for the assessment of the conformational transience of dissolved molecules while taking into account the effects of solvation. The free energy of oxytocin, which is a peptide hormone, as well as self-assembled ionic peptide complexes calculated using both the traditional RISM and the new RISM with average matrix (RISM-AM) approach are estimated. The free energy of oxytocin calculated using RISM-AM shows that the statistical error does not exceed the error obtained by standard averaging of solutions in the RISM equation. Despite the somewhat ambiguous results obtained for ionic peptide self-assembly using RISM-AM with Lennard–Jones repulsion correction, this method can still be considered applicable for fast molecular dynamics analysis. Since the required computational power can be reduced by at least two orders of magnitude, the medium-matrix RISM is indeed a highly applicable tool for studying macromolecular conformations as well as corresponding solvation effects.