Molecular dynamics simulations to gain insights into the stability and morphologies of k3 oligomers from β2-microglobulin

Po Sheng Fang, Jian Hua Zhao, Hsuan Liang Liu, Kung Tien Liu, Jenn Tzong Chen, Hsin Yi Lin, Chih Hung Huang, Hsu Wei Fang

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

β2-Microglobulin (β2-m) forms amyloid fibrils in patients undergoing long-term hemodialysis. K3 peptide, a Ser20-Lys41 fragment of β2-m, has been known to form fibrils over a wide range of pH and solvent conditions. Recent solid-state NMR has revealed that K3 oligomer adopts a parallel U-shaped β-strand-turn-β-strand motif. In order to investigate the stability and morphologies of K3 oligomers with different sizes (dimer, trimer, and tetrameri and organizations (single and double layers), several all-atom molecular dynamics simulations were conducted at 310 K and pH 2 in water and 2, 2, 2-trifluoroethanol (TFE). For single-layered organizations, our results show that TFE destabilizes the stacking of K3 peptides due to the fact that TFE weakens the intermolecular hydrophobic interactions of K3 oligomers. In addition, we also identified that the loop region is stabilized by the hydrophobic cluster involving resides Y7, Fll, and I16. Our results further suggest that K3 tetramer is a potential minimal nucleus seed for the formation of K3 protofibrils. For dou-ble-layered organizations in water, our data demonstrate that K3 peptides can form various stable assemblies through different interfacial arrangements, such as NN, NC, and CC, by different driving forces. We further propose that the stacking of different interfaces between two facing β-sheets of K3 peptides could be related to different fibril morphologies, which is in good agreement with the previous experimental results, showing that K3 protofibrils associated to formed mature fibrils with a wide range of diameters from 4 to 15 nm when they were transferred from 20% (v/v) TFE to aqueous solution.

Original languageEnglish
Pages (from-to)549-559
Number of pages11
JournalJournal of Biomolecular Structure and Dynamics
Volume26
Issue number5
DOIs
Publication statusPublished - Jan 1 2009
Externally publishedYes

Fingerprint

Trifluoroethanol
Molecular Dynamics Simulation
Peptides
Water
Hydrophobic and Hydrophilic Interactions
Amyloid
Renal Dialysis
Seeds

Keywords

  • 2, 2, 2-trifluoroethanol (TFE)
  • Amyloid fibril
  • Hydrophobic interaction
  • K3 peptide
  • Molecular dynamics (MD) simulation
  • Morphology
  • β2-microglobulin (β2-m)

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Molecular dynamics simulations to gain insights into the stability and morphologies of k3 oligomers from β2-microglobulin. / Fang, Po Sheng; Zhao, Jian Hua; Liu, Hsuan Liang; Liu, Kung Tien; Chen, Jenn Tzong; Lin, Hsin Yi; Huang, Chih Hung; Fang, Hsu Wei.

In: Journal of Biomolecular Structure and Dynamics, Vol. 26, No. 5, 01.01.2009, p. 549-559.

Research output: Contribution to journalArticle

Fang, Po Sheng ; Zhao, Jian Hua ; Liu, Hsuan Liang ; Liu, Kung Tien ; Chen, Jenn Tzong ; Lin, Hsin Yi ; Huang, Chih Hung ; Fang, Hsu Wei. / Molecular dynamics simulations to gain insights into the stability and morphologies of k3 oligomers from β2-microglobulin. In: Journal of Biomolecular Structure and Dynamics. 2009 ; Vol. 26, No. 5. pp. 549-559.
@article{adcc23b8c2c04ddd943b57417dbdf7d7,
title = "Molecular dynamics simulations to gain insights into the stability and morphologies of k3 oligomers from β2-microglobulin",
abstract = "β2-Microglobulin (β2-m) forms amyloid fibrils in patients undergoing long-term hemodialysis. K3 peptide, a Ser20-Lys41 fragment of β2-m, has been known to form fibrils over a wide range of pH and solvent conditions. Recent solid-state NMR has revealed that K3 oligomer adopts a parallel U-shaped β-strand-turn-β-strand motif. In order to investigate the stability and morphologies of K3 oligomers with different sizes (dimer, trimer, and tetrameri and organizations (single and double layers), several all-atom molecular dynamics simulations were conducted at 310 K and pH 2 in water and 2, 2, 2-trifluoroethanol (TFE). For single-layered organizations, our results show that TFE destabilizes the stacking of K3 peptides due to the fact that TFE weakens the intermolecular hydrophobic interactions of K3 oligomers. In addition, we also identified that the loop region is stabilized by the hydrophobic cluster involving resides Y7, Fll, and I16. Our results further suggest that K3 tetramer is a potential minimal nucleus seed for the formation of K3 protofibrils. For dou-ble-layered organizations in water, our data demonstrate that K3 peptides can form various stable assemblies through different interfacial arrangements, such as NN, NC, and CC, by different driving forces. We further propose that the stacking of different interfaces between two facing β-sheets of K3 peptides could be related to different fibril morphologies, which is in good agreement with the previous experimental results, showing that K3 protofibrils associated to formed mature fibrils with a wide range of diameters from 4 to 15 nm when they were transferred from 20{\%} (v/v) TFE to aqueous solution.",
keywords = "2, 2, 2-trifluoroethanol (TFE), Amyloid fibril, Hydrophobic interaction, K3 peptide, Molecular dynamics (MD) simulation, Morphology, β2-microglobulin (β2-m)",
author = "Fang, {Po Sheng} and Zhao, {Jian Hua} and Liu, {Hsuan Liang} and Liu, {Kung Tien} and Chen, {Jenn Tzong} and Lin, {Hsin Yi} and Huang, {Chih Hung} and Fang, {Hsu Wei}",
year = "2009",
month = "1",
day = "1",
doi = "10.1080/07391102.2009.10507270",
language = "English",
volume = "26",
pages = "549--559",
journal = "Journal of Biomolecular Structure and Dynamics",
issn = "0739-1102",
publisher = "Adenine Press",
number = "5",

}

TY - JOUR

T1 - Molecular dynamics simulations to gain insights into the stability and morphologies of k3 oligomers from β2-microglobulin

AU - Fang, Po Sheng

AU - Zhao, Jian Hua

AU - Liu, Hsuan Liang

AU - Liu, Kung Tien

AU - Chen, Jenn Tzong

AU - Lin, Hsin Yi

AU - Huang, Chih Hung

AU - Fang, Hsu Wei

PY - 2009/1/1

Y1 - 2009/1/1

N2 - β2-Microglobulin (β2-m) forms amyloid fibrils in patients undergoing long-term hemodialysis. K3 peptide, a Ser20-Lys41 fragment of β2-m, has been known to form fibrils over a wide range of pH and solvent conditions. Recent solid-state NMR has revealed that K3 oligomer adopts a parallel U-shaped β-strand-turn-β-strand motif. In order to investigate the stability and morphologies of K3 oligomers with different sizes (dimer, trimer, and tetrameri and organizations (single and double layers), several all-atom molecular dynamics simulations were conducted at 310 K and pH 2 in water and 2, 2, 2-trifluoroethanol (TFE). For single-layered organizations, our results show that TFE destabilizes the stacking of K3 peptides due to the fact that TFE weakens the intermolecular hydrophobic interactions of K3 oligomers. In addition, we also identified that the loop region is stabilized by the hydrophobic cluster involving resides Y7, Fll, and I16. Our results further suggest that K3 tetramer is a potential minimal nucleus seed for the formation of K3 protofibrils. For dou-ble-layered organizations in water, our data demonstrate that K3 peptides can form various stable assemblies through different interfacial arrangements, such as NN, NC, and CC, by different driving forces. We further propose that the stacking of different interfaces between two facing β-sheets of K3 peptides could be related to different fibril morphologies, which is in good agreement with the previous experimental results, showing that K3 protofibrils associated to formed mature fibrils with a wide range of diameters from 4 to 15 nm when they were transferred from 20% (v/v) TFE to aqueous solution.

AB - β2-Microglobulin (β2-m) forms amyloid fibrils in patients undergoing long-term hemodialysis. K3 peptide, a Ser20-Lys41 fragment of β2-m, has been known to form fibrils over a wide range of pH and solvent conditions. Recent solid-state NMR has revealed that K3 oligomer adopts a parallel U-shaped β-strand-turn-β-strand motif. In order to investigate the stability and morphologies of K3 oligomers with different sizes (dimer, trimer, and tetrameri and organizations (single and double layers), several all-atom molecular dynamics simulations were conducted at 310 K and pH 2 in water and 2, 2, 2-trifluoroethanol (TFE). For single-layered organizations, our results show that TFE destabilizes the stacking of K3 peptides due to the fact that TFE weakens the intermolecular hydrophobic interactions of K3 oligomers. In addition, we also identified that the loop region is stabilized by the hydrophobic cluster involving resides Y7, Fll, and I16. Our results further suggest that K3 tetramer is a potential minimal nucleus seed for the formation of K3 protofibrils. For dou-ble-layered organizations in water, our data demonstrate that K3 peptides can form various stable assemblies through different interfacial arrangements, such as NN, NC, and CC, by different driving forces. We further propose that the stacking of different interfaces between two facing β-sheets of K3 peptides could be related to different fibril morphologies, which is in good agreement with the previous experimental results, showing that K3 protofibrils associated to formed mature fibrils with a wide range of diameters from 4 to 15 nm when they were transferred from 20% (v/v) TFE to aqueous solution.

KW - 2, 2, 2-trifluoroethanol (TFE)

KW - Amyloid fibril

KW - Hydrophobic interaction

KW - K3 peptide

KW - Molecular dynamics (MD) simulation

KW - Morphology

KW - β2-microglobulin (β2-m)

UR - http://www.scopus.com/inward/record.url?scp=66949159146&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=66949159146&partnerID=8YFLogxK

U2 - 10.1080/07391102.2009.10507270

DO - 10.1080/07391102.2009.10507270

M3 - Article

VL - 26

SP - 549

EP - 559

JO - Journal of Biomolecular Structure and Dynamics

JF - Journal of Biomolecular Structure and Dynamics

SN - 0739-1102

IS - 5

ER -