TY - JOUR
T1 - Conformational dynamics of human IAPP monomers
AU - Murphy, Ronan D.
AU - Conlon, Jennifer
AU - Mansoor, Tayyaub
AU - Luca, Sorin
AU - Vaiana, Sara
AU - Buchete, Nicolae Viorel
N1 - Funding Information:
We thank Robert B. Best for helpful discussions and Robert Tycko for kindly providing the coordinates of the molecular models of hIAPP protofilaments. We gratefully acknowledge financial support from the Irish Research Council for Science, Engineering and Technology (IRCSET) , and the use of computational facilities provided by the Irish Centre for High-End Computing (ICHEC).
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2012/6
Y1 - 2012/6
N2 - 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.
AB - 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.
KW - Conformational analysis
KW - Data-driven kinetic analysis
KW - Human Islet Amyloid Polypeptide (hIAPP)
KW - Molecular dynamics
KW - Type 2 diabetes
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U2 - 10.1016/j.bpc.2012.03.010
DO - 10.1016/j.bpc.2012.03.010
M3 - Article
C2 - 22609945
AN - SCOPUS:84861143943
VL - 167
SP - 1
EP - 7
JO - Biophysical Chemistry
JF - Biophysical Chemistry
SN - 0301-4622
ER -