Assessment of heat shock protein 90 and epidermal growth factor receptor inhibitory potential of natural compounds from <i>Calophyllum membranaceum</i> and <i>Leonurus sibiricus</i> via molecular dynamics simulations and binding free energy calculati

This study involves a comprehensive computational analysis to assess the potential of 20 recently identified phytochemicals derived from <i>Calophyllum membranaceum</i> and <i>Leonurus sibiricus</i> as HSP90 and EGFR TK inhibitors. The study is comprised of four distinct parts: (1) DFT calculations including geometry optimisations and molecular electrostatic potential map calculations, (2) molecular docking studies, (3) molecular dynamics simulations and binding free energy (MM-PBSA) calculations and (4) drug-likeness and ADME analyses. The results obtained were compared with those obtained for the reference drugs BIIB021 and Gefitinib. The study observed that the HSP90 binding energies of the studied natural compounds could reach up to −47.0 kcal/mol and the EGFR TK binding energies up to −34.5 kcal/mol. For the reference molecules BIIB021 and Gefitinib, these values were −28.6 and −29.0 kcal/mol, respectively. The findings indicate that the majority of the natural compounds under investigation exhibited higher HSP90 inhibition potential compared to the reference molecule. Additionally, one of the compounds demonstrated higher inhibition potential than the reference molecule Gefitinib, while two compounds exhibited EGFR TK inhibition potential comparable to that of the reference molecule.