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Gene. 2014 Apr 10;539(1):82-90. doi: 10.1016/j.gene.2014.01.056. Epub 2014 Feb 1.

Ensemble docking and molecular dynamics identify knoevenagel curcumin derivatives with potent anti-EGFR activity.

Author information

1
Bioinformatics Division, Institute of Cytology and Preventive Oncology, I-7 Sector-39, Noida 201301, India; Department of Bio & Nano Technology, Guru Jambheshwar University Science & Technology, Hisar, India.
2
Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab, India.
3
Bioinformatics Division, Institute of Cytology and Preventive Oncology, I-7 Sector-39, Noida 201301, India.
4
Department of Bio & Nano Technology, Guru Jambheshwar University Science & Technology, Hisar, India.
5
Bioinformatics Division, Institute of Cytology and Preventive Oncology, I-7 Sector-39, Noida 201301, India. Electronic address: smagarwal@yahoo.com.

Erratum in

  • Gene. 2014 Apr 25;540(1):131. Shrivastava, Shambhavi [corrected to Srivastavaa, Shambhavi].

Abstract

Epidermal growth factor receptor tyrosine kinase (EGFR-TK) is an attractive target for cancer therapy. Despite a number of effective EGFR inhibitors that are constantly expanding and different methods being employed to obtain novel compounds, the search for newer EGFR inhibitors is still a major scientific challenge. In the present study, a molecular docking and molecular dynamics investigation has been carried out with an ensemble of EGFR-TK structures against a synthetically feasible library of curcumin analogs to discover potent EGFR inhibitors. To resolve protein flexibility issue we have utilized 5 EGFR wild type crystal structures during docking as this gives improved possibility of identifying an active compound as compared to using a single crystal structure. We then identified five curcumin analogs representing different scaffolds that can serve as lead molecules. Finally, the 5 ns molecular dynamics simulation shows that knoevenagel condensate of curcumin specifically C29 and C30 can be used as starting blocks for developing effective leads capable of inhibiting EGFR.

KEYWORDS:

Curcumin; EGFR; Ensemble docking; Molecular dynamics; Tyrosine kinase

PMID:
24491504
DOI:
10.1016/j.gene.2014.01.056
[Indexed for MEDLINE]

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