Affinity comparison of different THCA synthase to CBGA using modeling computational approaches

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Title	Affinity comparison of different THCA synthase to CBGA using modeling computational approaches
Authors	Moulay Abdelaziz El Alaoui^1,2, Azeddine Ibrahimi³, Oussama Semlali³, Zineb Tarhda³, Melloul Marouane^{1, 2}, Alaoui Najwa³, Abdelmajid Soulaymani² & Elmostafa El Fahime¹*
Affiliation	¹Functional Genomic Platform, UATRS, Center for Scientific and Technical Research [CNRST], Rabat, Morocco; ²Laboratory of Genetics and Biometry, Faculty of Sciences, University Ibn Tofail; ³MedBiotech Lab, Faculté de Médecine et de Pharmacie de Rabat, Université Mohammed V Souissi
Email	elfahime@cnrst.ma; *Corresponding author
Article Type	Hypothesis
Date	Received November 17, 2013; Revised December 24, 2013; Accepted January 06, 2014; Published January 29, 2014
Abstract	The ∆9-Tetrahydrocannabinol (THCA) is the primary psychoactive compound of Cannabis Sativa. It is produced by ∆1-Tetrahydrocannabinolic acid synthase (THCA) which catalyzes the oxidative cyclization of cannabigerolic acid (CBGA) the precursor of the THCA. In this study, we were interested by the three dimensional structure of THCA synthase protein. Generation of models were done by MODELLER v9.11 and homology modeling with ∆1-tetrahydrocannabinolic acid (THCA) synthase X ray structure (PDB code 3VTE) on the basis of sequences retrieved from GenBank. Procheck, Errat, and Verify 3D tools were used to verify the reliability of the six 3D models obtained, the overall quality factor and the Prosa Z-score were also used to check the quality of the six modeled proteins. The RMSDs for C-alpha atoms, main-chain atoms, side-chain atoms and all atoms between the modeled structures and the corresponding template ranged between 0.290 A°-1.252 A°, reflecting the good quality of the obtained models. Our study of the CBGA-THCA synthase docking demonstrated that the active site pocket was successfully recognized using computational approach. The interaction energy of CBGA computed in ‘fiber types’ proteins ranged between -4.1 95 kcal/mol and -5.95 kcal/mol whereas in the ‘drug type’ was about -7.02 kcal/mol to -7.16 kcal/mol, which maybe indicate the important role played by the interaction energy of CBGA in the determination of the THCA level in Cannabis Sativa L. varieties. Finally, we have proposed an experimental design in order to explore the binding energy source of ligand-enzyme in Cannabis Sativa and the production level of the THCA in the absence of any information regarding the correlation between the enzyme affinity and THCA level production. This report opens the doors to more studies predicting the binding site pocket with accuracy from the perspective of the protein affinity and THCA level produced in Cannabis Sativa.
Keywords	Cannabis Sativa, Homology modeling, Tetrahydrocannabinolic acid synthase potency, THC synthase binding energy, dynamic study, experimental design.
Citation	*El Alaoui et al.* Bioinformation 10(1): 033-038 (2014)
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.