Skip to main content
Open Access Publications from the University of California

UC Irvine

UC Irvine Previously Published Works bannerUC Irvine

Heparin-Assisted Amyloidogenesis Uncovered through Molecular Dynamics Simulations.


Glycosaminoglycans (GAGs), in particular, heparan sulfate and heparin, are found colocalized with Aβ amyloid. They have been shown to enhance fibril formation, suggesting a possible pathological connection. We have investigated heparin's assembly of the KLVFFA peptide fragment using molecular dynamics simulation, to gain a molecular-level mechanistic understanding of how GAGs enhance fibril formation. The simulations reveal an exquisite process wherein heparin accelerates peptide assembly by first "gathering" the peptide molecules and then assembling them. Heparin does not act as a mere template but is tightly coupled to the peptides, yielding a composite protofilament structure. The strong intermolecular interactions suggest composite formation to be a general feature of heparin's interaction with peptides. Heparin's chain flexibility is found to be essential to its fibril promotion activity, and the need for optimal heparin chain length and concentration has been rationalized. These insights yield design rules (flexibility; chain-length) and protocol guidance (heparin:peptide molar ratio) for developing effective heparin mimetics and other functional GAGs.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View