Affinity comparison of different THCA synthase to CBGA using modeling computational approaches |
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Authors: | Moulay Abdelaziz El Alaoui Azeddine Ibrahimi Oussama Semlali Zineb Tarhda Melloul Marouane Alaoui Najwa Abdelmajid Soulaymani Elmostafa El Fahime |
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Institution: | 1.Functional Genomic Platform, UATRS, Center for Scientific and Technical Research [CNRST], Rabat, Morocco;2.Laboratory of Genetics and Biometry, Faculty of Sciences, University Ibn Tofail;3.MedBiotech Lab, Faculté de Médecine et de Pharmacie de Rabat, Université Mohammed V Souissi |
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Abstract: | The Δ9-Tetrahydrocannabinol (THCA) is the primary psychoactive compound of Cannabis Sativa. It is produced by Δ1-
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. |
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Keywords: | Cannabis Sativa Homology modeling Tetrahydrocannabinolic acid synthase potency THC synthase binding energy dynamic study experimental design |
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