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Applied Biochemistry and Biotechnology

, Volume 160, Issue 6, pp 1723–1733 | Cite as

In Silico Identification of Significant Detrimental Missense Mutations of EGFR and Their Effect with 4-Anilinoquinazoline-Based Drugs

  • R. Rajasekaran
  • Rao Sethumadhavan
Article

Abstract

In this work, we identified the detrimental missense mutations (point mutations) in epidermal growth factor receptor (EGFR) and its binding efficiency with the inhibitors namely Erlotinib, Gefitinib, and Lapatinib. Out of 26 point mutations on EGFR, 12 point mutations were commonly less stable, deleterious, and damaged as shown by all the three servers, I-Mutant2.0, SIFT, and PolyPhen. Further, we modeled 12 mutants and superimposed with the native EGFR to get RMSD values. Docking studies showed that Erlotinib had lesser binding affinity against both native and all the 12 mutants. Gefitinib had maximum binding affinity only with two mutants, viz., R748P and L858R. Lapatinib had maximum binding affinity with both native and other 10 mutants. Based on our computational analysis, we recommend that the combined administration of Gefitinib and Lapatinib could give a better effect in combating the disease.

Keywords

Point mutation EGFR Erlotinib Gefitinib Lapatinib 

Notes

Acknowledgment

The authors thank the management of Vellore Institute of Technology for providing the facilities to carry out this work.

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Copyright information

© Humana Press 2009

Authors and Affiliations

  1. 1.Bioinformatics Division, School of Biotechnology, Chemical and Biomedical EngineeringVellore Institute of TechnologyTamil NaduIndia

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