Influence of C-terminal residues on the structural and molecular properties of dipeptides: a theoretical study in a vacuum and implicit and explicit aqueous environments

The role of C-terminal residues in influencing the structural and molecular properties of a set of six dipeptides was studied using the B3LYP/6-31++G(d,p) level of theory in a vacuum and implicit and explicit aqueous environment. The dipeptides were constructed by keeping pyrrolysine as a fixed component in the N-terminus whereas the component in the C-terminus was varied with six different combinations, viz. Val, Ile, Glu, Thr, Gln, and Lys. The C-terminal residues were chosen on the basis of the propensity of their side chain moieties to be in contact with a polar solvent like water. Frequency calculations on the fully optimized molecular geometries of the dipeptides confirmed them to be true minima. The HOMO/LUMO energies as well as their energy gaps, rotational constants, dipole moments, and theoretically predicted vibrational spectra of all the dipeptides were thoroughly analyzed. The identity of the varying C-terminal residue affects the value of the ϕ dihedral, planarity of the peptide plane, and geometry around the α-carbon atoms of a given dipeptide. Solvation effects of the implicit aqueous environment are found to modify the gas-phase conformation of a dipeptide around the angle ψ and influence the number and types of intramolecular H-bonds occurring in a dipeptide structure. The influence of the explicit aqueous environment is evident on the geometrical parameters associated with the geometries of amide planes and vibrational spectra of the dipeptides. Graphical abstract