Combined experimental and computational investigation of vildagliptin: spectroscopy, electronic structure, MD and Docking to EGFR, VEGFR2, and HER2 anticancer targets

This study combines experimental and computational approaches to investigate the molecular geometry and physicochemical properties of vildagliptin (VILD). Using methods such as UV-Vis, spectrofluorimetry, FTIR/Raman, and circular dichroism alongside DFT, molecular docking, and dynamics simulations, a reliable molecular model was obtained that aligns closely with X-ray crystallographic data. This model enabled accurate predictions of vibrational frequencies and systematic assignments of vibrational modes. Analyses, including Hirshfeld surface mapping, molecular electrostatic potential, HOMO-LUMO energetics, Fukui indices, and natural population analysis, provided clear insights into VILD’s reactivity, while NBO and TD-DFT studies elucidated key stabilizing interactions and high-energy electronic transitions. NTO visualization further clarified orbital dynamics, and circular dichroism measurements explained the molecular basis of the Cotton effect. Additionally, molecular docking and molecular dynamics simulations confirmed the formation of stable complexes with EGFR, VEGFR2, and HER2 receptor proteins, suggesting potential anticancer activity. The main purpose of this publication is to fill existing gaps in our understanding of VILD’s molecular behavior and offer a robust foundation for rational drug design and improved therapeutic strategies.