Heme prevents amyloid beta peptide aggregation through hydrophobic interaction based on molecular dynamics simulation

Area of Science:

• Biochemistry
• Neuroscience
• Molecular Biology

Background:

• Heme is crucial for various biological functions, including electron transfer and oxygen transport.
• Amyloid-beta (Aβ) peptide aggregation into higher-order oligomers is a central pathological hallmark of Alzheimer's disease (AD).

Purpose of the Study:

• To investigate the formation of Aβ-heme complexes and their role in inhibiting Aβ aggregation.
• To identify the dominant binding motifs between Aβ peptides and heme.

Main Methods:

• Conventional molecular dynamics simulations were employed.
• Simulations were performed on systems with varying ratios of Aβ peptides to heme (1 Aβ + 1 heme and 2 Aβ + 4 hemes).

Main Results:

• Several dominant binding motifs between Aβ peptides and heme were identified.
• Hydrophobic residues of Aβ peptides demonstrated a high affinity for heme, rather than histidine residues.
• Hydrophobic interactions were found to play a dominant role in Aβ-heme complex formation.

Conclusions:

• Aβ-heme complex formation is essential for inhibiting Aβ aggregation, a key pathway in Alzheimer's disease.
• Hydrophobic interactions are the primary drivers of Aβ-heme complex formation.
• This interaction indirectly prevents Aβ aggregation, offering a potential neuroprotective mechanism.