title: Heme prevents amyloid beta peptide aggregation through hydrophobic interaction based on molecular dynamics simulation.
abstract: Heme, which is abundant in hemoglobin and many other hemoproteins, is known to play an important role in electron transfer, oxygen transport, regulation of gene expression, and many other biological functions. With the belief that the aggregation of Aβ peptides forming higher order oligomers is one of the central pathological pathways in Alzheimer's disease, the formation of the Aβ-heme complex is essential as it inhibits Aβ aggregation and protects the neurons from degradation. In our studies, conventional molecular dynamics simulations were performed on the 1 Aβ + 1 heme and 2 Aβ + 4 hemes system, respectively, with the identification of several dominant binding motifs. We found that hydrophobic residues of the Aβ peptide have a high affinity to interact with heme instead of the histidine residue. We conclude that hydrophobic interaction plays a dominant role in the Aβ-heme complex formation which indirectly serves to physically prevent Aβ aggregation.
authors.affiliation: School of Physical and Mathematical Sciences, Nanyang Technological University, Nanyang Link 21, Singapore.
authors.forename: Li Na
authors.initials: LN
authors.lastname: Zhao
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Mu
authors.forename: Lock Yue
authors.initials: LY
authors.lastname: Chew
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D016000:Cluster Analysis; D006418:Heme / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D006418:Heme