| dc.description.abstract | In this study, a systemic analysis of the new protein database was performed. A dataset of 2,058 non-homogenous protein structures with resolutions of x-ray diffraction better than 2.0 Å were extracted from the currently released protein data bank (PDB). The propensities of 19 non-glycl amino acids at different main-chain conformations were calculated. The results show that the asparagine (Asn) as well as some polar amino acids prefers to occur at the higher energy alpha-L conformation. In particular, the Asn has the highest propensity. The result was reported in the previous literatures based on the analysis of fewer protein structures. However, the reasons which lead to such result are not clear. This study employed the bioinformatics analysis and quantum chemical calculations to study the roles of some important interactions such as hydrogen-bonding, solvation energy, and dipole-dipole interactions in stabilizing the Asn at alpha-L conformation.
The results show that hydrogen-bond percentage of Asn at alpha-L conformation is lower than that at alpha-R and beta-conformations indicating the hydrogen bonding is not the major stabilizing energy source. The solvation energies estimated from the B3LYP/6-31G(d,p) level with polarizable continuum (PCM) solvation models show the solvents with different polarities can stabilize the Asn at alpha-L conformation. The database analysis also shows similar results where the Asn at alpha-L conformation has higher solvent accessible surface area (SASA) than that at other conformations. However, due to the complicated environments of Asn in protein matrix, the strength of the solvation can not be calculated accurately.
More interestingly, the gas phase quantum chemical calculations show the populations of Asn at alpha-L conformation is higher than Ala at alpha-L conformation. The results of these “environment free” calculations hint for that the Asn can stabilize itself with alpha-L conformation, may arise from its unique side chain. Further analysis shows that the carbonyl-carbonyl dipole-dipole interactions of the Asn main chain and side chain can stabilize the alpha-L conformation. In contrast, such interaction can destabilize the alpha-R conformation due to the fact of alpha-L and alpha-R conformations being mirror images. This interaction stabilizes the alpha-L conformation, at the same time, destabilizes the alpha-R conformation, decreasing their energy difference and resulting in the highest propensity of Asn at alpha-L conformation.
In conclusion, Asn at alpha-L conformation can be stabilized by the solution. Additionally, the propensity of Asn at alpha-L conformation is enhanced by the carbonyl dipole-dipole interactions of main and side chains. | en_US |