GGXGG Peptide Propensities
D-amino acids have properties that make them desirable drug and vaccine targets. Using a GGXGG host-guest pentapeptide system, we performed exhaustive sampling of the conformational propensities for both L- and D- amino acids. [1,2] Knowledge of such propensities can inform peptide design. These simulations included D-allo-isoleucine and D-allo-threonine, which are the forms of isoleucine and threonine obtained in vivo through α-epimerization, where the original side chain chiralities are retained. The total simualtion time 6.6 μ-seconds. The simulations were again performed according to our standard Dynameomics Protocol.
Table 1: Conformational sampling propensities of L- and D- GGXGG peptide simulations.
| Propensity Table for GGXGG Peptide Simulations (%) |
|---|
| L-Isoform |
D-Isoform |
|---|
| Res. |
αR |
nαR |
αL |
nPβ |
PIIL |
PIR |
Other |
Res. |
DαR |
DnαR |
DαL |
DnPβ |
DPIIL |
DPIR |
Other |
|---|
| ALA-1 | 23.6 | 26.2 | 4.4 | 10.9 | 9.1 | 6.4 | 19.4 | ALA-1 | 22.4 | 24.9 | 11.7 | 9.1 | 7.3 | 6.0 | 18.7 |
| ALA-2 | 23.5 | 27.4 | 5.7 | 9.3 | 7.5 | 6.7 | 19.9 | ALA-2 | 22.8 | 23.8 | 9.9 | 9.2 | 8.9 | 5.9 | 19.6 |
| ALA-3 | 25.0 | 27.6 | 6.6 | 8.5 | 7.4 | 5.9 | 19.0 | ALA-3 | 24.7 | 28.3 | 4.1 | 8.7 | 7.3 | 7.0 | 19.9 |
| ARG | 28.1 | 29.8 | 7.1 | 8.3 | 9.1 | 3.0 | 14.5 | ARG | 29.5 | 30.2 | 7.4 | 7.9 | 8.7 | 2.4 | 13.9 |
| ASN | 40.2 | 34.6 | 1.6 | 7.6 | 4.7 | 2.6 | 8.5 | ASN | 39.7 | 34.9 | 4.1 | 7.0 | 3.3 | 2.7 | 8.3 |
| ASP | 30.6 | 42.2 | 5.5 | 2.4 | 0.2 | 4.9 | 14.2 | ASP | 26.0 | 35.4 | 11.9 | 4.7 | 0.4 | 6.4 | 15.2 |
| ASH | 40.0 | 39.6 | 3.1 | 5.4 | 1.8 | 2.4 | 7.7 | ASH | 36.9 | 31.1 | 9.9 | 8.4 | 3.3 | 2.8 | 7.6 |
| CYS | 28.6 | 33.3 | 5.8 | 8.5 | 7.0 | 3.8 | 12.9 | CYS | 22.6 | 26.3 | 12.1 | 9.9 | 10.5 | 3.6 | 15.1 |
| GLN | 26.7 | 25.5 | 13.5 | 8.6 | 9.1 | 2.8 | 13.8 | GLN | 28.9 | 28.0 | 6.5 | 9.1 | 10.5 | 3.2 | 14.0 |
| GLU | 31.8 | 23.7 | 5.8 | 10.0 | 11.6 | 2.8 | 14.4 | GLU | 33.1 | 24.6 | 3.0 | 10.6 | 11.9 | 3.0 | 3.0 |
| GLH | 28.2 | 24.8 | 11.3 | 9.4 | 9.1 | 3.6 | 13.6 | GLH | 26.9 | 33.9 | 5.5 | 7.6 | 6.1 | 4.2 | 15.9 |
| GLY | 16.7 | 5.5 | 9.8 | 3.4 | 3.3 | 1.5 | 59.9 | GLY | - | - | - | - | - | - | - |
| HID | 24.6 | 33.1 | 8.1 | 9.2 | 7.2 | 3.6 | 14.1 | HID | 24.9 | 31.8 | 10.5 | 9.3 | 7.2 | 2.8 | 13.5 |
| HIE | 30.9 | 30.4 | 4.7 | 8.2 | 10.7 | 1.8 | 13.3 | HIE | 29.2 | 26.7 | 6.7 | 10.0 | 12.3 | 2.3 | 12.8 |
| HIP | 15.3 | 41.0 | 5.4 | 8.9 | 2.6 | 8.4 | 18.4 | HIP | 12.4 | 45.6 | 0.0 | 9.9 | 1.8 | 10.3 | 20.0 |
| ILE | 16.3 | 29.4 | 0.0 | 11.1 | 19.6 | 1.6 | 21.9 | ILE | 15.8 | 40.7 | 0.2 | 13.2 | 15.3 | 2.1 | 12.7 |
| A-ILE | - | - | - | - | - | - | - | A-ILE | 32.7 | 26.1 | 0.9 | 10.9 | 16.4 | 1.3 | 11.7 |
| LEU | 35.9 | 27.4 | 4.3 | 8.3 | 10.5 | 1.6 | 11.9 | LEU | 38.2 | 28.0 | 2.1 | 8.1 | 10.7 | 1.7 | 11.2 |
| LYS | 32.8 | 32.8 | 4.2 | 7.0 | 7.0 | 2.1 | 14.1 | LYS | 31.7 | 31.4 | 3.8 | 7.9 | 8.2 | 2.7 | 14.3 |
| MET | 31.0 | 27.8 | 10.2 | 7.4 | 7.9 | 2.6 | 13.0 | MET | 31.4 | 29.5 | 1.3 | 10.2 | 10.7 | 3.2 | 13.6 |
| PHE | 29.0 | 35.5 | 1.3 | 10.3 | 9.8 | 2.8 | 11.4 | PHE | 29.8 | 35.1 | 5.9 | 7.9 | 6.8 | 2.4 | 12.1 |
| PRO | 17.4 | 0.0 | 0.0 | 15.8 | 59.2 | 0.0 | 7.6 | PRO | 4.9 | 0.0 | 0.0 | 16.3 | 70.3 | 0.0 | 8.4 |
| SER | 28.3 | 17.0 | 4.0 | 12.1 | 21.0 | 2.1 | 15.5 | SER | 27.4 | 16.0 | 2.2 | 12.3 | 23.8 | 2.2 | 16.0 |
| THR | 41.5 | 21.7 | 1.6 | 9.1 | 14.2 | 0.9 | 11.1 | THR | 47.1 | 24.0 | 0.2 | 6.8 | 10.9 | 0.6 | 10.4 |
| A-THR | - | - | - | - | - | - | - | A-THR | 19.0 | 26.2 | 0.0 | 10.9 | 24.0 | 2.0 | 17.9 |
| TRP | 30.7 | 35.2 | 6.4 | 6.7 | 6.0 | 2.2 | 12.7 | TRP | 29.9 | 38.0 | 4.9 | 7.3 | 6.3 | 1.8 | 11.8 |
| TYR | 23.5 | 32.5 | 8.7 | 9.7 | 7.8 | 2.9 | 13.2 | TYR | 31.0 | 36.6 | 5.2 | 7.2 | 6.5 | 2.1 | 11.5 |
| VAL | 21.7 | 28.3 | 3.8 | 11.4 | 18.6 | 1.8 | 14.5 | VAL | 17.2 | 23.7 | 0.2 | 15.4 | 27.1 | 1.9 | 14.5 |
Labeling conventions used for the specific conformations in L-amino acids: right-handed α-helix (αR), left-handed α-helix (αL), polyproline type II left-handed helix (PIIL), polyproline type I right-handed helix (PIR), and the non-polyproline β-region (nPβ).
The corresponding regions for D-amino acids reflected across the inversion point of Ramachandran space: right-handed α-helix (DαR), left-handed α-helix (DαL), polyproline type II left-handed helix (DPIIL), polyproline type I right-handed helix (DPIR), and the non-polyproline β-region (DnPβ).
A-ILE and A-THR refer to allo-isoleucine and allo-threonine respectively. For futher details, please refer to the articles referenced below.
References
- Towse, C.-L., Hopping, G., Vulovic, I., Daggett, V. Nature versus design: The conformational propensities of D-amino acids and the importance of side chain chirality. Protein Engineering, Design, and Selection, 2014. [DOI]
- Beck D.A.C., Alonso D.O.V., Inoyama D., and Daggett V. The intrinsic conformational propensities of the 20 naturally occurring amino acids and reflection of these propensities in proteins. Proceedings of the National Academy of Sciences USA 105: 12259-12264, 2008. [DOI]