Human apolipoprotein B100 protein prediction and modeling of the interaction with the alkaloid methyl cytisine by molecular docking.

BUCCI, ANTONELLA; FRIAS, M.A.; LEDESMA A E

Congreso; 12vo Congreso Argentino de Bioinformática y Biología Computacional; 2022

Background: Low-density lipoprotein (LDL) particles are the main carriers of cholesterol in humanplasma. The organization of the particle, which is composed of apolar lipids and a monolayer ofphospholipids stabilized by apolipoprotein B100 (Apo-B100), as recognized by LDL receptors, is highly complex and still unknown. ApoB 100 is an extremely large protein (4563 amino acids) and very little is known about its structure, different experimental approaches to resolve the tertiary structure of LDL, have the inconvent of a complex particle organization. Reports of isoquinoline-type alkaloids, such as berberine (benzyltetrahidroxyquinoline), have demonstrated their potential as an antihyperlipidemic agent by reducing serum levels of cholesterol, triglycerides, and LDL cholesterol due to its antioxidant activity by inhibition of LDL lipid peroxidation.Results: Five domains were also reported in terms of trypsin accessible peptides. the sequence data reported in UNIPROT for each domain, structure prediction corresponding to lipoprotein domains was modeled using the I-TASSER, and AlphaFold2 server. The structure of the ligand N-Methyl-cytisine, (NMC), alkaloid was previously obtained in our group. The 3D structure of apolipoprotein B100 was generated sequentially (eeach domain), the set of domains was obtained by calculating protein-protein coupling using the HADDOCK2.2 web server. From this result, the structure of the complete protein was validated using the graphic server Ramachandran observed that 85% of residues falling in the highly favorable zones. The secondary structure predicted by the YASARA program.Conclusions: The binding site between the N-methyl cytisine with each domain of apolipoprotein B100 and were studied by molecular docking using the AutoDock 4.2 program, the free binding energy of the I domain presents the lowest value independently of the rest of the protein, which indicates that this site is the most probably site for interaction, this current The residues involved in the interaction were characterized, finding polar and hydrophobic residues as responsible for the stabilization of the complex with the NMC alkaloid. More studies are being carried out to evaluate its effect in the oxidative process of apolipoprotein B100.