Back to Journals » OncoTargets and Therapy » Volume 8

Determination and validation of mTOR kinase-domain 3D structure by homology modeling

Authors Lakhlili W, Chevé G, Yasri A, Ibrahimi A

Received 8 March 2015

Accepted for publication 6 May 2015

Published 30 July 2015 Volume 2015:8 Pages 1923—1930

DOI https://doi.org/10.2147/OTT.S84200

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 5

Editor who approved publication: Dr Faris Farassati


Wiame Lakhlili,1 Gwénaël Chevé,2 Abdelaziz Yasri,2 Azeddine Ibrahimi1

1Laboratoire de Biotechnologie (MedBiotech), Faculté de Médecine et de Pharmacie de Rabat, Université Mohammed V de Rabat, Rabat, Morroco; 2OriBase Pharma, Cap Gamma, Parc Euromédecine, Montpellier, France

Abstract: The AKT/mammalian target of rapamycin (mTOR) pathway is considered as one of the commonly activated and deregulated signaling pathways in human cancer. mTOR is associated with other proteins in two molecular complexes: mTOR complex 1/Raptor and the mTOR complex 2/Rictor. Using the crystal structure of the related lipid kinase PI3Kγ, we built a model of the catalytic region of mTOR. The modeling of the three-dimensional (3D) structure of the mTOR was performed by homology modeling program SWISS-MODEL. The quality and validation of the obtained model were performed using PROCHECK and PROVE softwares. The overall stereochemical property of the protein was assessed by the Ramachandran plot. The model validation was also done by docking of known inhibitors. In this paper, we describe and validate a 3D model for the mTOR catalytic site.

Keywords: mTOR, homology modeling, mTOR kinase-domain, docking

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]