Conformational dynamics of human IAPP monomers

Ronan D. Murphy, Jennifer Conlon, Tayyaub Mansoor, Sorin Luca, Sara M. Vaiana, Nicolae Viorel Buchete

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

We study the conformational dynamics of the human Islet Amyloid Polypeptide (hIAPP) molecule - a 37 residue-long peptide associated to type 2 diabetes - using molecular dynamics (MD) simulations. We identify partially structured conformational states of the hIAPP monomer, categorized by both end-to-end distance and secondary structure, as suggested by previous experimental and computational studies. The MD trajectories of hIAPP are analyzed using data-driven methods, in particular principal component analysis, in order to identify preferred conformational states of the amylin monomer and to discuss their relative stability as compared to corresponding states in the amylin dimer. These potential hIAPP conformational states could be further tested and described experimentally, or in conjunction with modern computational analysis tools such as Markov state-based methods for extracting kinetics and thermodynamics from atomistic MD trajectories.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalBiophysical Chemistry
Volume167
DOIs
StatePublished - Jun 2012

Fingerprint

Islet Amyloid Polypeptide
Monomers
Molecular Dynamics Simulation
Molecular dynamics
Trajectories
Medical problems
Principal Component Analysis
Thermodynamics
Dimers
Principal component analysis
Type 2 Diabetes Mellitus
Peptides
Molecules
Kinetics
Computer simulation

Keywords

  • Conformational analysis
  • Data-driven kinetic analysis
  • Human Islet Amyloid Polypeptide (hIAPP)
  • Molecular dynamics
  • Type 2 diabetes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Organic Chemistry

Cite this

Murphy, R. D., Conlon, J., Mansoor, T., Luca, S., Vaiana, S. M., & Buchete, N. V. (2012). Conformational dynamics of human IAPP monomers. Biophysical Chemistry, 167, 1-7. https://doi.org/10.1016/j.bpc.2012.03.010

Conformational dynamics of human IAPP monomers. / Murphy, Ronan D.; Conlon, Jennifer; Mansoor, Tayyaub; Luca, Sorin; Vaiana, Sara M.; Buchete, Nicolae Viorel.

In: Biophysical Chemistry, Vol. 167, 06.2012, p. 1-7.

Research output: Contribution to journalArticle

Murphy, RD, Conlon, J, Mansoor, T, Luca, S, Vaiana, SM & Buchete, NV 2012, 'Conformational dynamics of human IAPP monomers', Biophysical Chemistry, vol. 167, pp. 1-7. https://doi.org/10.1016/j.bpc.2012.03.010
Murphy RD, Conlon J, Mansoor T, Luca S, Vaiana SM, Buchete NV. Conformational dynamics of human IAPP monomers. Biophysical Chemistry. 2012 Jun;167:1-7. https://doi.org/10.1016/j.bpc.2012.03.010
Murphy, Ronan D. ; Conlon, Jennifer ; Mansoor, Tayyaub ; Luca, Sorin ; Vaiana, Sara M. ; Buchete, Nicolae Viorel. / Conformational dynamics of human IAPP monomers. In: Biophysical Chemistry. 2012 ; Vol. 167. pp. 1-7.
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