Vibrational spectroscopic characterization, quantum chemical, molecular docking and molecular dynamics investigations of cyclo(L-phenylalanyl-L-proline), an anticancer agent

The molecular structure and spectral properties of cyclo(L-Phenylalanyl-L-Proline) dipeptide, which has several biological activities, were investigated. Firstly, conformational preference of the cyclo(L-Phenylalanyl-L-Proline) was searched and obtained lowest energy conformer of the cyclic dipeptide was then optimized using Density Functional Theory with wb97xd/6-311++G(d,p) level of theory. A detailed vibrational spectral analysis has been carried out and assignments of the fundamental modes have been proposed. The experimental vibrational wavenumbers of the investigated compound display good agreement with the computed values. The Frontier Molecular Orbitals, Molecular Electrostatic Potential and electronic transitions of the investigated compound were discussed. In addition, the ¹H and ¹³C NMR chemical shifts of the cyclic dipeptide were calculated and the results were compared with the experimental values. Also, to evaluate the anticancer potential, molecular docking studies of cyclo(L-Phenylalanyl-L-Proline) within the ATP-binding sites of both wild type (EGFR^WT; ID: 4HJO) and mutant (EGFR^T790M; ID: 3W2O) Epidermal Growth Factor Receptor were performed. The results indicated that cyclo(Phe-Pro) has high binding affinities toward both EGFR^WT (−6.6 kcal/mol) and EGFR^T790M (−7.7 kcal/mol) receptors, thus, has good anticancer activity and also has potential to overcome drug resistance in therapy. Molecular dynamics simulations on cyclo(L-Phenylalanyl-L-Proline)-wild type complex were conducted through a 50-nanosecond timed to investigate the ligand-receptor interactions in more detail, and to determine the binding free energy accurately. The binding free energy of the cyclo(L-Phenylalanyl-L-Proline)-wild type complex was calculated to be −27.18 kcal/mol.