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Title

Molecular docking and simulation of Curcumin with Geranylgeranyl Transferase1 (GGTase1) and Farnesyl Transferase (FTase)

 

Authors

Parasuraman Aiya Subramani1, 2, Venkata Ramireddy Narala2, R Dinakaran Michael1, Dakshayani Lomada3 & Madhava C Reddy4*

 

Affiliation

1Centre for Fish Immunology, School of Life Sciences, Vels University, Pallavaram, Chennai-600117, India; 2Department of Zoology, Yogi Vemana University, Kadapa; 3Department of Genetics and Genomics, Yogi Vemana University, Kadapa; 4Department of Biotechnology and Bioinformatics, Yogi Vemana University, Kadapa, Andhra Pradesh, India-516003

 

Email

cmadhavareddy@gmail.com; *Corresponding author

 

Article Type

Hypothesis

 

Date

Received March 24, 2015; Revised May 04, 2015; Accepted May 05, 2015; Published May 28, 2015

 

Abstract

Protein prenylation is a posttranslational modification that is indispensable for translocation of membrane GTPases like Ras, Rho, Ras etc. Proteins of Ras family undergo farnesylation by FTase while Rho family goes through geranylgeranylation by GGTase1. There is only an infinitesimal difference in signal recognition between FTase and GGTase1. FTase inhibitors mostly end up selecting the cells with mutated Ras proteins that have acquired affinity towards GGTase1 in cancer microcosms. Therefore, it is of interest to identify GGTase1 and FTase dual inhibitors using the docking tool AutoDock Vina. Docking data show that curcumin (from turmeric) has higher binding affinity to GGTase1 than that of established peptidomimetic GGTase1 inhibitors (GGTI) such as GGTI-297, GGTI-298, CHEMBL525185. Curcumin also interacts with FTase with binding energy comparable to co-crystalized compound 2-[3-(3-ethyl-1-methyl-2-oxo-azepan-3-yl)-phenoxy]-4-[1-amino-1-(1-methyl-1h-imidizol-5-yl)-ethyl]-benzonitrile (BNE). The docked complex was further simulated for 10 ns using molecular dynamics simulation for stability. Thus, the molecular basis for curcumin binding to GGTase1 and FTase is reported.

 

Keywords

Prenylation, GGTase1, Rho, AutoDock Vina, Curcumin, Molecular dynamics simulations, FTase

 

Citation

Subramani et al.   Bioinformation 11(5): 248-253(2015)
 

Edited by

P Kangueane

 

ISSN

0973-2063

 

Publisher

Biomedical Informatics

 

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.