Figure 1: Images of compounds and active site of BACE1. Compounds are in purple, residues within five angstroms of the compound are in green, and water molecules are in red
Figure 2 shows BACE1 protein-protein interactions to better understand its basic biology and contribution to Alzheimer’s Disease pathology. The figure focused on examining these interactions in terms of hydrogen bonds formed and measured the number of polar contacts formed and the distance between them. The compounds 3, 8b, 7, and 6b have a high number of polar bonds formed. Compounds 3, 4-piperidine, and 6b have a short distance between polar contact, meaning the bond formed would be stronger. Understanding the strength of hydrogen bonds can show how well the compounds work in attaching to BACE1. PDB number 2OHN seems to have the strongest bond formed in relation to the hydrogen bonds of all analyzed PDB.
Conclusion Based on what could be found from the results, PDB number 2OHN forms a stronger hydrogen bond than the other examples. The strength of the inhibitor affects the way BACE1 is able to release certain amounts of amyloid fibers; in the case of PDB 2OHN, the leaving portion of BACE1 will not be able to cut APPn at all, and will not be able to release amyloid fiber. Thus, while studying these interactions between BACE1 and other inhibitors is helpful in learning more about Alzeihmer’s Disease pathology, relying on the inhibitors is not a viable solution in stopping the amyloid fibers being tangled up. After all, a healthy amount of peptide being released from BACE1 cuts is vital for some particularly important neural function.
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