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Heparin-Assisted Amyloidogenesis Uncovered through Molecular Dynamics Simulations

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Heparin-Assisted Amyloidogenesis Uncovered through Molecular Dynamics Simulations. / Khurshid, Beenish; Rehman, Ashfaq Ur; Luo, Ray et al.

In: ACS Omega, Vol. 7, No. 17, 03.05.2022, p. 15132-15144.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

Khurshid, B, Rehman, AU, Luo, R, Khan, A, Wadood, A & Anwar, J 2022, 'Heparin-Assisted Amyloidogenesis Uncovered through Molecular Dynamics Simulations', ACS Omega, vol. 7, no. 17, pp. 15132-15144. https://doi.org/10.1021/acsomega.2c01034

APA

Khurshid, B., Rehman, A. U., Luo, R., Khan, A., Wadood, A., & Anwar, J. (2022). Heparin-Assisted Amyloidogenesis Uncovered through Molecular Dynamics Simulations. ACS Omega, 7(17), 15132-15144. https://doi.org/10.1021/acsomega.2c01034

Vancouver

Khurshid B, Rehman AU, Luo R, Khan A, Wadood A, Anwar J. Heparin-Assisted Amyloidogenesis Uncovered through Molecular Dynamics Simulations. ACS Omega. 2022 May 3;7(17):15132-15144. Epub 2022 Apr 21. doi: 10.1021/acsomega.2c01034

Author

Khurshid, Beenish ; Rehman, Ashfaq Ur ; Luo, Ray et al. / Heparin-Assisted Amyloidogenesis Uncovered through Molecular Dynamics Simulations. In: ACS Omega. 2022 ; Vol. 7, No. 17. pp. 15132-15144.

Bibtex

@article{e38b0887ffef4947a13a0198488ac6e8,
title = "Heparin-Assisted Amyloidogenesis Uncovered through Molecular Dynamics Simulations",
abstract = "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{\textquoteright}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{\textquoteright}s interaction with peptides. Heparin{\textquoteright}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.",
keywords = "General Chemical Engineering, General Chemistry",
author = "Beenish Khurshid and Rehman, {Ashfaq Ur} and Ray Luo and Alamzeb Khan and Abdul Wadood and Jamshed Anwar",
year = "2022",
month = may,
day = "3",
doi = "10.1021/acsomega.2c01034",
language = "English",
volume = "7",
pages = "15132--15144",
journal = "ACS Omega",
issn = "2470-1343",
publisher = "American Chemical Society",
number = "17",

}

RIS

TY - JOUR

T1 - Heparin-Assisted Amyloidogenesis Uncovered through Molecular Dynamics Simulations

AU - Khurshid, Beenish

AU - Rehman, Ashfaq Ur

AU - Luo, Ray

AU - Khan, Alamzeb

AU - Wadood, Abdul

AU - Anwar, Jamshed

PY - 2022/5/3

Y1 - 2022/5/3

N2 - 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.

AB - 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.

KW - General Chemical Engineering

KW - General Chemistry

U2 - 10.1021/acsomega.2c01034

DO - 10.1021/acsomega.2c01034

M3 - Journal article

VL - 7

SP - 15132

EP - 15144

JO - ACS Omega

JF - ACS Omega

SN - 2470-1343

IS - 17

ER -