title: Affinity comparison of different THCA synthase to CBGA using modeling computational approaches.
abstract: The Δ(9-)Tetrahydrocannabinol (THCA) is the primary psychoactive compound of Cannabis Sativa. It is produced by Δ(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 Δ1-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 Å-1.252 Å, 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.
authors: Functional Genomic Platform, UATRS, Center for Scientific and Technical Research [CNRST], Rabat, Morocco ; Laboratory of Genetics and Biometry, Faculty of Sciences, University Ibn Tofail.
authors: Moulay Abdelaziz El
authors: MA
authors: Alaoui
authors: MedBiotech Lab, Faculté de Médecine et de Pharmacie de Rabat, Université Mohammed V Souissi.
authors: Azeddine
authors: A
authors: Ibrahimi
authors: MedBiotech Lab, Faculté de Médecine et de Pharmacie de Rabat, Université Mohammed V Souissi.
authors: Oussama
authors: O
authors: Semlali
authors: MedBiotech Lab, Faculté de Médecine et de Pharmacie de Rabat, Université Mohammed V Souissi.
authors: Zineb
authors: Z
authors: Tarhda
authors: Functional Genomic Platform, UATRS, Center for Scientific and Technical Research [CNRST], Rabat, Morocco ; Laboratory of Genetics and Biometry, Faculty of Sciences, University Ibn Tofail.
authors: Melloul
authors: M
authors: Marouane
authors: MedBiotech Lab, Faculté de Médecine et de Pharmacie de Rabat, Université Mohammed V Souissi.
authors: Alaoui
authors: A
authors: Najwa
authors: Laboratory of Genetics and Biometry, Faculty of Sciences, University Ibn Tofail.
authors: Abdelmajid
authors: A
authors: Soulaymani
authors: Functional Genomic Platform, UATRS, Center for Scientific and Technical Research [CNRST], Rabat, Morocco.
authors: Elmostafa El
authors: EE
authors: Fahime
keywords: Cannabis Sativa; Homology modeling; THC synthase binding energy; Tetrahydrocannabinolic acid synthase potency; dynamic study; experimental design