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Oligoglycine
Appendix
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Gly1
Structure
(a) in the figure at right corresponds to the most stable conformer of
GlyH+ obtained by DFT calculations using a B3LYP/6-311G** basis
set. The dihedral angle α is 0° [see depiction
in (b)], but rotation about the C-N axis does not appear to be severely
hindered, since the conformation with α=60°
is only 1 kcal/mol higher in energy. For GlyNa+ two structures
are possible, one with the sodium ion bound to neutral glycine in its
amino acid form [structure (c)], and one with Na+ bound to
zwitterionic glycine [structure (d)]. A full geometry optimization on
a MP2/6-311++G** level indicates, that the first form (c) is some 3.6
kcal/mol more stable than the second one (d) after zero point energy correction.
The much faster DFT B3LYP/6-311++G**calculation agrees with the MP2 result
within 0.3 kcal/mol. The structures found by molecular
modeling are with minor deviations the same as the ab initio conformations.
The single minima located for GlyH+ (α=60°)
and GlyNa+ (zwitterion; α=0°) correspond
to the structures shown above. For Na+ bound to Gly in its
amino acid form three minima were found, the lowest one being that shown
in structure (c) above.
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Gly2
Molecular
mechanics calculations indicate that diglycine ionized at the N-terminus,
Gly2H+ [structure (a) in figure at right] and Gly2Na+
[structure (b)], prefer a cyclic arrangement as depicted for structure
(a). The corresponding extended linear conformations are ~7 kcal/mol higher
in energy. Note, that the dihedral angle ω
along the peptide bond, which usually is ~180° ("trans") in any oligoglycine
or other peptide systems, is ~0° ("cis") for the lowest-energy conformers
in both of these dimer systems. In this arrangement the protonated N-terminus
can be better solvated by the C-terminal oxygen. The sodiated glycine
form (c) is determined by the solvation of Na+ by the two >C=O
groups. The terminal -NH2 is either also bound to Na+
or forms a hydrogen bond with the amide hydrogen as shown in (c), the
latter structure being ~1.5 kcal/mol more stable. DFT calculations on
Gly2Na+ indicate at all levels of theory, that form
(c) is more stable by more than 10 kcal/mol than form (b).
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GlynH+,
n=3-6
Semiempirical
geometry optimizations carried out on structures obtained from molecular
mechanics calculations for Gly4H+ and Gly5H+
indicate that salt bridge structures of the form I are substantially less
stable than simple charge solvation structures of type II.
![](glyxh%2B.gif)
Thus,
for energetic reasons protonated oligoglycines of the form I can be excluded
as possible candidate structures not only for the small Gly2H+
and Gly3H+, but also when the chain is long enough
to allow separation of the two positive charges and formation of a salt
bridge between the positive N-terminus and the negative C-terminus. Molecular
mechanics results indicate that protonated oligoglycines prefer a
cyclic arrangement where one of the N-terminal amino hydrogens forms a
hydrogen bond to the C-terminal >C=O group (see figure below). Some
of the amide >C=O groups are also
bound to the N-terminus to help solvate the charge. The lowest-energy
conformers are held together by three such H-bonds, which fold the peptide
into a pretty spherical shape. More extended conformers are typically
higher in energy and there is a reasonable correlation between the energy
of a conformation and its calculated cross section or degree of unfolding.
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GlynNa+,
n=3-6
The
GlynNa+ structures (where Glyn is a non-zwitterion)
obtained by molecular
mechanics are determined by the solvation of Na+ by >C=O.
Even for the hexamer, all >C=O groups can coordinate around the Na+
ion, but the lowest-energy conformers (for n=4-6) have 4 to 5 such electrostatic
O-Na bonds. This is still a large coordination number and combined with
the rather long O-Na bonds of 2.3 to 2.5 Å, it causes the relatively
small peptide to unfold and span around Na+ like an open umbrella,
resulting in a quite oblate shape (see figure below).
![](gly5na.gif)
The
conformers of zwitterionic oligoglycine bound to Na+ are all
fairly compact. In all cases we were able to locate only a small number
of different conformers using our simulated annealing procedure, and in
all cases there exists one particularly stable conformation, shown in
the figure below for Gly5Na+. All of those "salt
bridge" conformers have in common that both Na+ and -NH3+
are bound to the carboxylate group via an electrostatic bond and 1 or
2 H-bonds, respectively. The amide >C=O groups coordinate either to
Na+ or to -NH3+. The coordination number
for Na+ is typically 4 (3 for n=3), and
-NH3+ forms between 2 (for n=3,4) to 3 (for n=6)
hydrogen bonds.
![](gly5nazw.gif)
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