In-silico molecular docking study of novel derivatives of erlotinib in glioma

Abstract

Gliomas are primary brain tumours arises from the glial cells. Gliomas associated risk factor depend upon its degree of stage and grade. Erlotinib is a quinazoline derivative and antineoplastic agent that capacities as a Protein Kinase Inhibitor for Epidermal growth factor receptor (EGFR) related tyrosine kinase and widely used for treating non-small cell carcinoma. Erlotinib, (a tyrosine kinase inhibitor) has been found in the glioblastoma. ErbB (EGF family receptor tyrosine kinase) established to control cell survival, proliferation, migration, and differentiation. The ErbB receptor accounts for the restricted and redundant functions in the maintenance of tissues in adult mammals. Newly discovered drug targets and personalised treatments could be used to identify the characteristics of any individual’s tumorigenesis. To see the binding mode of deferent classes of erlotinib carefully chosen based on the structural comparison, we employed simulated screening and molecular docking based on the theory of evolution. The study consists of a simulated screening of around 3200 molecular derivatives of erlotinib and their molecular docking using a Lamarckian genetic algorithm. Molecular docking results showed binding energy ranging from -12.15 kcal/mol to -1.17 kcal/mol. Top 10 best-docked proteins were analyzed using UCSF Chimera and finding discovered the complicated atomic-scale properties between ligand and the target protein. Further wet lab study requires to study the actual binding as binding mode provided. To identify new inhibitors of EGFR with higher potency and specificity, additional information is needed for future designs molecules.