Quantum Density Functional Theory Studies on Additive Hydration of Tuftsin Tetrapeptide

Density functional B3LYP method has been used to study the molecular properties of the tuftsin tetrapeptide (threonine-lysine-proline-arginine) and its retro form (arginine-proline-lysine-threonine). The influence of single water molecule on the conformations and relative stabilities of solvated tuftsin complexes has been studied by placing the water molecule at the individual amino acid residues of both the tuftsin complexes. The contribution of four water molecules to the system energetics of tuftsin complexes has also been analyzed. The conformational changes occurred in the solvated tuftsin complexes have been explored through their dihedral angles. The tuftsin is found to be sensitive to structural changes, and our results indicate that water-tuftsin hydrogen bonds (H-bonds), in addition to intramolecular H-bonds, stabilize the β-turn structure with H-bonds between threonine and arginine residues of tuftsin. Difference in the stability of the hydrated complexes is confined to the amino acid residues at which the water molecule is attached to tuftsin. The interaction energy calculations have been used to investigate the strength of the intermolecular H-bond interactions. The AIM theory and NBO analysis were employed to survey the H-bonding patterns in hydrated tuftsin complexes. The maximum ellipticity value (0.129) is noted for the Cα-H (Arg)…O (W) interaction in Tuftsin…4W complex which indicates the higher chance of structural deformation under external perturbations. The interactions between oxygen lone pairs in water and C-H antibond orbitals of tuftsin and retro tuftsin complexes exist with E2 in the range of 4.03-5.7 and 3.59-4.14 kcal/mol, respectively.