Metal ion binding of the alpha-gamma hybrid cyclic peptide nanotubes--a theoretical study based on the ONIOM method.

The quantum mechanics/molecular mechanics ONIOM calculations have been performed to study the structure and metal-ion binding properties of all-trans cyclo[1R-3S-gamma-Acc-Gly]3 hexapeptide nanotube (TAG)3PNT. The intersubunit distances and tube angle of (TAG)3PNT exhibited the sturdy nature of (TAG)3 stacks upon Li+ , K+ , Mg2+, and Zn2+ enclosure.The calculated dimer binding energies of (TAG)3PNT and its ionic complexes confirm that the building blocks are bound by C=O...H-N hydrogen bond interactions. The binding energy of (TAG)3PNT with ions interacting at the surface cavity exhibit the affinity of ions at the entrance of the channel and the many-body analysis for the ion interacting at the central region substantiates the major contribution of two-body interactions to the total binding energy. In general, the binding energies of (TAG)3PNT metal ion interacting complexes with well-maintained channel shows alpha-gamma hybrid cyclic peptides as the promising peptidic nanochannels of biological interests.

Structural and dynamical studies of all-trans and all-cis cyclo[(1R,3S)-gamma-Acc-Gly]3 peptides.

The quantum chemical and molecular dynamics studies have been performed to infer the structural changes of all-trans and all-cis forms of cyclo[(1R,3S)-3-aminocyclohexanecarboxylicacid(gamma-Acc)-alpha-Glycine(Gly)](3) hexapeptide. The backbone conformations of the above peptide have been analyzed using the valence and peptide deformation angles applying B3LYP/6-311G** level of theory. The conformational preference of the backbone of all-trans and all-cis cyclo[(1R,3S)-gamma-Acc-Gly](3) hexapeptides is found to depend on the puckering of cyclohexane rings. The non-uniform distribution of water inside the cavity is observed, where sometimes water molecules formed a chain like conformation through hydrogen bond networks while traversing the pore of all-cis cyclo[(1R,3S)-gamma-Acc-Gly](3) peptide. Larger relaxation times of the order of a hundred to two hundred pico seconds for active site...water hydrogen bond interactions were noticed. The hydrophobic nature of the cavity of all-trans cyclo[(1R,3S)-gamma-Acc-Gly](3) due to the presence of cyclohexane moiety has been analyzed. Further this investigation emphasized on the non-transport of molecules through the pore of all-trans cyclo[(1R,3S)-gamma-Acc-Gly](3) peptide due to the obstruction produced by cyclohexane groups.