Evolución de la variación estructural del receptor endocannabinoide CB1 frente a candidatos endógenos y exógenos

Abstract

The determination of the response of the endocannabinoid CB1 receptor against modulators of biological activity was carried out through In silico techniques of computational chemistry; The behavior of the receptor without ligand and with five selected ligands was generally taken into account (Rimonabant, Anandamide, Tetrahydrocannabinol, AA06, and AE09). The massive molecular docking and docking technique was used for the location of each ligand in the active site of the receptor using the Autodock vina and molecular dynamics software for the analysis of the structure using the GROMACS software and the CHARMM force field, where the dynamic behavior The system is obtained through the interactions of stretching, bending and torsion of the receptor. It was determined that by analyzing the non-binding interactions between each ligand and the amino acids of the system it is not enough to determine the biological activity of the evaluated candidates. It is found that the receptor region with the greatest structural variation throughout molecular dynamics is made up of intracellular loop 3, as well as the variation of the receptor's secondary structure as a result of interaction with the different ligands evaluated, where the greatest loss of secondary structure, it was associated with candidate AA06, which was established as a potential antagonist against candidate AE09 as a potential agonist.