Structural Stability and Binding Efficiency of Strong and Weak Interactions in Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Domain of Human and Drosophila

Abstract

Epidermal growth factor receptor (EGFR) is a cell membrane receptor serving as a molecular target for Non Small Cell Lung cancer (NSCLC). The aim of the study was to analyze the weak ion interactions taking place in the tyrosine kinase domain of Human and Drosophila EGFR. This study throws light on the environment preferability, stabilizing residues taking part in weak and strong interactions of EGFR TK domain. Analysis of short, medium and long range contacts showed that the cation-� interactions are mainly formed by long-range contacts, whereas CH…OC interactions are formed by both long and short range interactions. Except Pro, other non-polar hydrophobic amino acids in Drosophila EGFR TK domain were present in buried environment. However, in humans other than Pro and Ala, which were involved in SS (CH…OC) and SM (NH…OC) interactions, other non-polar hydrophobic amino acid preferred to be in buried environment. The results observed in this study will be useful for understanding the contribution of weak and strong interactions to the stability of EGFR TK domain. Further, the weak interactions have distinct roles in the stability of EGFR TK domain in addition to other conventional strong interactions. The results can lead to the identification of novel targets for NSCLC drugs which in turn will serve as a major break through in the treatment of NSCLC. methoxy-6-(3-morpholin-4-ylpropoxy)quinazolin-4-amine), both orally available, low molecular weight, reversible and selective EGFR-TKIs, were used as advanced EGFR- targeted drugs in NSCLC treatment. They blocked signal