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Heat shock protein 90 (HSP90) is one of the most attractive targets for research on cancer treatment, and nowadays, many studies carried out for the development of effective HSP90 inhibitors. In the current study, recently published ten natural compounds have been investigated using computer aided drug design (CADD) approach. The study consists of three parts; (1) density functional theory (DFT) calculations including geometry optimizations, vibrational analyses, and molecular electrostatic potential (MEP) map calculations, (2) molecular docking and molecular dynamics (MD) simulations, and (3) binding energy calculations. In DFT calculations, Becke three-parameter hybrid functional with Lee-Yang-Parr correlation functional (B3LYP) and 6-31 + G(d,p) basis set were used. After performing molecular docking calculations, top-scoring ligand-receptor complexes were subjected to MD simulations for 100 ns to investigate the stability of the ligand-receptor complexes and the interactions in more detail. Finally, in binding energy calculations molecular mechanics with Poisson-Boltzmann surface area (MM-PBSA) method was used. The results showed that five of the investigated ten natural compounds have higher binding affinity to HSP90α than that of reference drug Geldanamycin, and could be promising compounds for future studies.Communicated by Ramaswamy H. Sarma.

Phytochemicals are important chemical compounds in pharmaceutical chemistry. These natural compounds have interesting biological activities, including anticancer, as well as many other functions. EGFR (epidermal growth factor receptor) tyrosine kinase inhibition is emerging as one of the accepted methods in the treatment of cancer. On the other hand, computer-aided drug design has become an increasingly important field of study due to its many important advantages such as efficient use of time and other resources. In this study, fourteen phytochemicals which have triterpenoid structure and have recently entered the literature were investigated computationally for their potential as EGFR tyrosine kinase inhibitors. In the study, DFT (density functional theory) calculations, molecular docking, molecular dynamics simulations, binding free energy calculations with the use of MM-PBSA (molecular mechanics Poisson-Boltzmann Surface Area) method, and ADMET predictions were performed. The obtained results were compared to the results obtained for reference drug Gefitinib. Results showed that the investigated natural compounds are promising structures for EGFR tyrosine kinase inhibition.Communicated by Ramaswamy H. Sarma.