In silico Molecular Docking and Molecular Dynamics Simulation Analysis of Matairesinol with Molecular Targets in Non-Small Cell Lung Carcinoma

Background

Lung cancer is the most reported cancer worldwide and therapeutic resistance poses a major challenge. This in silico molecular docking and molecular dynamic simulation study was carried out to evaluate the binding affinity and stability of molecular interactions between the phytochemical Matairesinol and the molecular targets in Non-Small Cell Lung Carcinoma (NSCLC) which are implicated in the pathogenesis and development of therapeutic resistance, thereby exploring its potential anticancer activity in NSCLC.

Materials and Methods

The three-dimensional structure of Matairesinol was obtained from the PubChem database. The three-dimensional protein structures of target proteins were obtained from Protein Data Bank. DOCK6 software package was used for the preparation of ligands and proteins. For the molecular dynamics study, the OPLS-2005 force field implemented in Desmond routine of Schrödinger software suite was used and the study was performed till 100 ns. Binding free energy (MM/ GBSA), Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuation (RMSF) values of all complexes were determined. Principal component analysis and Detailed Cross-Correlation Maps were carried out.

Results and Discussion

Matairesinol showed good binding energies and docking scores with all the targets tested in this study with relatively stable molecular interactions, with the highest affinity shown towards ALK. The interactions with EGFR wild type, KRAS G12C mutant protein, VEGFR2, C-MET and ALK were especially of high stability.

Conclusion

The results of this study reveal the potential anti-cancer activity of Matairesinol in NSCLC with the possible added benefit of treating therapeutic resistance. Further studies are required to fully evaluate the target profile of Matairesinol in NSCLC and its therapeutic efficacy.