Conformational dynamics of human IAPP monomers

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. [Display omitted] ► Kinetic clustering of conformational states of human IAPP monomers. ► Partially structured hIAPP conformational states correspond to several end-to-end distances. ► Conformational dynamics of hIAPP monomers and dimers driven by hydrophobic packing. ► PCA as an unbiased, data-driven approach to identify conformational states.