Secondary Structure Effectson the Acidity of Histidine and Lysine-Based PeptidesModel; A Theoretical Study

چکیده مقاله

In this study, the effect of the secondary structure of the protein on the acid strength of three structures of random(R), alpha helix (α) and beta sheet()were investigatedtheoretically . These structures are relatedto the cationic amino acids of histidine and lysine in the polypeptidechain of eight-glycine residue. Computationalmethods at the HF, B3LYP, X3LYP and M05-2Xlevelsin the gas and solution phases were applied. Implicit CPCM solvation model and explicit 2-layer ONIOM methods for the computations in solution were used withthe 6-31G (d) basis set. Comparison of pK a values of histidine-based peptideshows that acid strength is accordedto: > α> R, while in the case of lysine, acid strength is accordanceto: α > > R. Based on theobtained data, ONIOM method is unable to predict the pKa values in the explicit solvation model. NBO analysis showed that one of the main reasons for the increase in the acidity of the solution phaseis the increasein delocalization energy difference(ΔEdelocal) of the neutral acid and the corresponding cation.Topological analysis of quantum theory of atoms in moleculesfor the electron charge density at the bond critical points of the hydrogen bonds of the secondary structures in the presence of the solvent does not show a meaningfulcorrelation with the interaction energyor acid strength. The absolute average ratio of 1.37 and 1.34 for the kinetic energy density to the local potential energy density of lysine and histidine-based peptides, respectively ,reveals the non-covalent nature of the O … H bonds.Finally, based on the obtained results, pK a of the proteins can be predicted as a function of hydrogen bond characters and their delocalization energy differences between the cationic and neutral forms.