Human islet amyloid polypeptide(hIAPP)is an intrinsically disordered peptide,whose amyloid fibrils are found in 90%patients of type 2 diabetes.Cellular membrane,especially that composed of negatively-charged lipids,accelerates the hIAPP amyloid fibrillation.Meanwhile,the membrane integrity is also disrupted during the hIAPP aggregation.Recent computational studies have shed light on the structural ensemble of membrane-bound hIAPP [1].In this work,we focus on the conformational dynamics of hIAPP monomer on POPG membrane bilayer,via μs-long all-atom molecular dynamics simulations.Starting from the random-coiled structures in water solute,hIAPP tends to form secondary structures upon binding to the membrane surface in tens of ns.Moreover,the α-helical hIAPP further inserts into the head-tail interface of POPG membrane,while the β-hairpin resides on the POPG surface,during 1.6-μs-long simulations.The insertion of α-helix undergoes the breakage and reformation of its hydrogen-bonds,and induces hydrophobic defects in the membrane.Meanwhile,the β-hairpin causes the bending of membrane surface,and results in stronger membrane thinning and disordering.The dynamics of lipid rotation and water hydrogen bonding are greatly retarded during the hIAPP binding process.Interestingly,both the α-helical and β-sheet hIAPP structures become more extended upon the membrane adsorption.The coexistence of both α and β structures in the membrane-bound hIAPP monomer is consistent with the multiple complementary mechanisms proposed by previous experiments,indicating the complexity of the hIAPP aggregation pathways under membrane environment.