Molecular dynamic of the complexes of $\mathrm{(RADA)_4}$ – the self-organizing ionic peptides

In this study we investigated the properties of peptide complexes, which form the structure of protofibrils capable of the assembly into a filament. Using the method of molecular dynamic the data were obtained for the conformational states of di-, tetra-, octa- and dodecamer in explicit water, which allowed us to identify the structure, which might be responsible for self-assembly of ionic peptide molecules. It was shown, the conformational lability of individual molecules is reduced not only by increasing the total number of peptides in the complexes, but also in cases where the polypeptide chain is located in the central area of the protofilament, and thusly more “insulated” from the contacts with a solvent. According to the results of molecular modeling (MD) the $\mathrm{H\text-(RADA)_4\text-OH}$ complexes it appears that increasing size of supramolecular structures leads to increased stability of antiparallel $\beta$-structures and intramolecular hydrogen bonds on the time interval of 10 ns. It was shown the greater fluctuations of atomic coordinates of the peptide backbone correspond to the amino acid residues located on terminal flanks of the peptide molecules. Conclusion was made that the minimally sufficient structure of a protofilament could be as small as tetramer of $\mathrm{H\text-(RADA)_4\text-OH}$ in $\beta$-conformation, while the peptides are situated in antiparallel mode. The same is true for the complexes of a higher level, whose assembly is directed by the key role played by distinctive hydrophobic interactions of the alanine residues which form an “inner layer” of tetramers and/or the greater structures of the emerging filament as well.