Investigate the protein-ligand binding affinity and evaluate the receptor binding abilities of different classes of ligands for APOE4 through molecular docking studies. The polymorphic nature of human Apo E gene encodes one of 3 common epsilon (ε) alleles (ε2, ε3, and ε4), reported to influence the risk of cardiovascular diseases. Structural basis of APOE4 involvement in CAD suggests that the intramolecular domain interactions to be a suitable target for therapeutic intervention. Identification of APOE4 modulators, targeted towards therapeutic candidates in CAD using Molecular Docking studies. Various classes of ligands including known drugs used in the treatment of CAD, fragment-based stabilizers and their similar structures and molecules with known bioactivity against APOE4 were screened for their binding affinity and further investigated for their interactions with APOE4. Computational studies show the benzyl amide derived structures to be useful candidates in modulation of APOE4. The protein-ligand binding affinities predicted in the study indicated receptor binding abilities of APOE4 that can lead to have interesting insights on structural conformity of APOE4 and its correlated functional aspects. Understanding modulation of APOE4 can pave ways to use it as biomarker for CAD as well as for its therapeutics. Further analysis of the variation of the docked protein structure, molecular dynamic simulation can be performed to generate a dynamic structure for binding analysis.

A significant genetic suspect for coronary artery disease is the pathological adaptation of apolipoprotein E4 (APOE4) through intramolecular interaction. With the prevailing evidence on APOE4 genotype and its prevalence in coronary artery disease, the present study has investigated the protein-ligand binding affinity and unveil the receptor binding abilities of different classes of ligands for APOE4 through molecular docking studies. Structural basis of APOE4 involvement in CAD suggests that the intramolecular domain interactions to be a suitable target for therapeutic intervention. Various classes of ligands including known drugs used in the treatment of CAD, fragment-based stabilizers and their similar structures and molecules with known bioactivity against APOE4 were screened for their binding affinity and further investigated for their interactions with APOE4. Computational studies show the benzyl amide derived structures to be useful candidates in modulation of APOE4. The dynamics of the binding analysis can be further achieved with an in-depth understanding of drug-receptor interactions performing molecular dynamic simulation studies.