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

Lakhlili W, Chevé G, Yasri A, Ibrahimi A - Onco Targets Ther (2015)

Bottom Line: The quality and validation of the obtained model were performed using PROCHECK and PROVE softwares.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire de Biotechnologie (MedBiotech), Faculté de Médecine et de Pharmacie de Rabat, Université Mohammed V de Rabat, Rabat, Morroco.

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.

No MeSH data available.


Related in: MedlinePlus

VERIFY-3D plot analysis of computed mTOR 3D model.Abbreviations: mTOR, mammalian target of rapamycin; 3D, three-dimensional; 1D, one-dimensional.
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f1-ott-8-1923: VERIFY-3D plot analysis of computed mTOR 3D model.Abbreviations: mTOR, mammalian target of rapamycin; 3D, three-dimensional; 1D, one-dimensional.

Mentions: After the first evaluation with Swiss-Model Server, the model was assessed by VERIFY-3D.19 Verify3D analyzes the compatibility of an atomic model (3D) with its own amino acid sequence (1D). Each residue is assigned a structural class based on its location and environment (alpha, beta, loop, polar, nonpolar, etc). A collection of good structures is used as a reference to obtain a score for each of the 20 amino acids in this structural class. The scores (from −1 to +1) were added and plotted for individual residues. The residues falling in the area where the orange line crosses 0.0 have low prediction accuracy and less stable conformation20,21 as shown in Figure 1.


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

Lakhlili W, Chevé G, Yasri A, Ibrahimi A - Onco Targets Ther (2015)

VERIFY-3D plot analysis of computed mTOR 3D model.Abbreviations: mTOR, mammalian target of rapamycin; 3D, three-dimensional; 1D, one-dimensional.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4525790&req=5

f1-ott-8-1923: VERIFY-3D plot analysis of computed mTOR 3D model.Abbreviations: mTOR, mammalian target of rapamycin; 3D, three-dimensional; 1D, one-dimensional.
Mentions: After the first evaluation with Swiss-Model Server, the model was assessed by VERIFY-3D.19 Verify3D analyzes the compatibility of an atomic model (3D) with its own amino acid sequence (1D). Each residue is assigned a structural class based on its location and environment (alpha, beta, loop, polar, nonpolar, etc). A collection of good structures is used as a reference to obtain a score for each of the 20 amino acids in this structural class. The scores (from −1 to +1) were added and plotted for individual residues. The residues falling in the area where the orange line crosses 0.0 have low prediction accuracy and less stable conformation20,21 as shown in Figure 1.

Bottom Line: The quality and validation of the obtained model were performed using PROCHECK and PROVE softwares.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire de Biotechnologie (MedBiotech), Faculté de Médecine et de Pharmacie de Rabat, Université Mohammed V de Rabat, Rabat, Morroco.

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.

No MeSH data available.


Related in: MedlinePlus