Comparison of Molecular Dynamics Simulation Tools: EGFR-Gefitinib Complex as a Case Study

Non-small cell lung carcinoma (NSCLC) is the second most common cancer type worldwide. It is a type of lung malignancy that initially starts in the lung and may spread to other parts of the human body. Mutations in the epidermal growth factor receptor (EGFR), play a significant role in cell growth and malignancy. EGFR is also considered a major driver oncogene in NSCLC. Thus, several targeted drugs, like tyrosine kinase inhibitors (TKIs), i.e., Gefitinib, have been developed and approved by the FDA against the EGFR. Tyrosine kinase inhibitor (TKI) drug usage has shown an improved survival rate. However, the possibility of drug resistance threatens treatment plans and efficacy. Computational methods, such as, molecular dynamics simulation, have been developed to calculate the binding stability of WT and mutant EGFR. In this study, we investigate the performance of molecular dynamics simulation (MD simulation) tools - GROMACS, NAMD, and BioExcel - on the EGFR-Gefitinib complex, focusing on the catalytic site mutation G719S. The analysis of conformational changes in both WT and mutant EGFR-Gefitinib complexes after simulation revealed structural alterations. Comparative analysis across different time scales highlights the efficacy of NAMD and GROMACS over BioExcel, particularly evident in root mean square deviation and root mean square fluctuations. This investigation sheds light on the optimal use of MD simulation tools for studying large protein complexes, helping in the development of targeted therapies for NSCLC and other cancer types.