Equilibrium Geometry and Properties Of Cyclo[(Gly-d-Ala)₄] and {Cyclo[(Gly-d-Ala)₄]}₂ from Density Functional Theory

Abstract

Cyclic peptides containing even numbers of alternating D-and L-amino acids adopt a symmetric ring structure with NH and CO amide functions approximately perpendicular to the average plane of the ring. This results in hydrogen-bonded, -sheet like tubular ensembles by coaxial stacking of rings in which adjacent strands are oriented antiparallel to one another. Starting from a molecular mechanics minimum energy configuration having the C 4 symmetry reported for similar structures, an optimized monomer geometry which retained that symmetry was obtained using density functional theory (DFT). The geometry of the monomer is quite similar to that of stable polypeptides and proteins and the calculated gas-phase harmonic vibrational frequencies are quantitatively reasonable. Two monomers were then brought together coaxially, with adjacent strands arranged antiparallel, creating a dimer of D 4 symmetry. Dimer energy was then minimized with respect to ring separation along, and relative rotation of one ring with respect to the other about, the common C 4 axis. The interstrand separation in this dimer model is reasonable in comparison with experimental values reported for stable -sheet polypeptides and proteins as are the harmonic vibrational frequencies. An approximation to the harmonic N-H‚‚‚O stretching frequency calculated for this dimer model was also physically reasonable by comparison to the interchain motion calculated for -sheet polypeptides from analysis of experimental vibrational frequencies. Though synthesis of the molecules in this study has not been reported, they serve as excellent models for the analysis of ring structure and for isolating the role of backbone-backbone hydrogen bonds in the stacking process for similar assemblies. This study provides theoretical support for experimental work on more complex systems, and the DFT calculations are among the largest ever for the study of molecular systems using double valence single polarization basis sets.

Theoretical study of the interaction between sodium ion and a cyclopeptidic tubular structure

“…The optimized geometrical parameters of the monomer are given in Table1. The bond length values are similar to those reported for cyclo [(Gly‐D‐Ala) 4 ],13 with the largest deviation of 0.04 Å in the case of the CαC bond. Conversely, dihedral angles values are rather different, with the backbone torsional angle ω less planar than in cyclo [(Gly‐D‐Ala) 4 ].…”

“…The resulting main features of { cyclo [(Gly) 8 ]} 5 are the following: height, 20.1 Å; interring distance, 4.8 Å, very close to the experimental values found in several cyclopeptide nanotubes;1, 3, 13 and diameter of the cavity (central monomer), 9.1 Å.…”

Studies on the Structure and Stability of Cyclic Peptide Based Nanotubes Using Oligomeric Approach: A Computational Chemistry Investigation

“…Bragin and co-workers have applied the DFT method to study the equilibrium structure and electronic properties of {cyclo[Gly-D-Ala] 4 } 2 . 55 The geometrical parameters and interaction energy of the monomer and dimer CPs consisting of cyclo[L-Phe-D-Ala] 4 have been computed using semiempirical and DFT-based methods. 56 The same type of calculations have been carried out to characterize the energetic and structural properties of cyclo[(-3 -HGly) 4 -] and its oligomers.…”

Structure and stability of cyclic peptide based nanotubes: a molecular dynamics study of the influence of amino acid composition

“…[1][2][3][4] The structural characteristics of CPs in a cyclic peptide nanotube (CPNT) have been investigated using various experimental techniques and theoretical methods. 1,4,[5][6][7][8][9][10][11][12][13][14][15][16] The backbone carbonylamide functionality of CP aligns with the tube axis, thereby stabilizing the self-assembly through H-bonding interactions. The stacking of CPs with opposite orientation, i.e.…”