The aggregation of human islet amyloid polypeptide (hIAPP) can damage the membrane of the beta-cells in the pancreatic islets and induce type 2 diabetes (T2D). Growing evidences indicated that the major toxic species are small oligomers of IAPP. Due to the fast aggregation nature, it is hard to characterize the structures of IAPP oligomers by experiments, especially in the complex membrane environment. On the other side, molecular dynamics simulation can provide atomic details of the structure and dynamics of the aggregation of IAPP. In this study, all-atom bias-exchange metadynamics (BE-Meta) and unbiased molecular dynamics simulations were employed to study the structural properties of IAPP dimer in the membranes environments. A number of intermediates, including alpha-helical states, beta-sheet states, and fully disordered states, are identified. The formation of N-terminal beta-sheet structure is prior to the C-terminal beta-sheet structure towards the final fibril-like structures. The alpha-helical intermediates have lower propensity in the dimeric hIAPP and are off-pathway intermediates. The simulations also demonstrate that the beta-sheet intermediates induce more perturbation on the membrane than the alpha-helical and disordered states and thus pose higher disruption ability.
机构:
NYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USANYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Abedini, Andisheh
;
Plesner, Annette
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Pathol & Lab Med, Child & Family Res Inst, Vancouver, BC, Canada
Univ British Columbia, Dept Surg, Vancouver, BC, Canada
Novo Nordisk AS, Bagsvaerd, DenmarkNYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Plesner, Annette
;
Cao, Ping
论文数: 0引用数: 0
h-index: 0
机构:
SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USANYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Cao, Ping
;
Ridgway, Zachary
论文数: 0引用数: 0
h-index: 0
机构:
SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USANYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Ridgway, Zachary
;
Zhang, Jinghua
论文数: 0引用数: 0
h-index: 0
机构:
NYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USANYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Zhang, Jinghua
;
Tu, Ling-Hsien
论文数: 0引用数: 0
h-index: 0
机构:
SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USANYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Tu, Ling-Hsien
;
Middleton, Chris T.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Wisconsin, Dept Chem, Madison, WI 53706 USA
Phase Tech Spect Inc, Madison, WI USANYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Middleton, Chris T.
;
Chao, Brian
论文数: 0引用数: 0
h-index: 0
机构:
NYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USANYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Chao, Brian
;
Sartori, Daniel J.
论文数: 0引用数: 0
h-index: 0
机构:
NYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USANYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Sartori, Daniel J.
;
Meng, Fanling
论文数: 0引用数: 0
h-index: 0
机构:
SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USANYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Meng, Fanling
;
Wang, Hui
论文数: 0引用数: 0
h-index: 0
机构:
SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USANYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Wang, Hui
;
Wong, Amy G.
论文数: 0引用数: 0
h-index: 0
机构:
SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USANYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Wong, Amy G.
;
Zanni, Martin T.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Wisconsin, Dept Chem, Madison, WI 53706 USANYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Zanni, Martin T.
;
Verchere, C. Bruce
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Pathol & Lab Med, Child & Family Res Inst, Vancouver, BC, Canada
Univ British Columbia, Dept Surg, Vancouver, BC, CanadaNYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Verchere, C. Bruce
;
Raleigh, Daniel P.
论文数: 0引用数: 0
h-index: 0
机构:
SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USANYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Raleigh, Daniel P.
;
Schmidt, Ann Marie
论文数: 0引用数: 0
h-index: 0
机构:
NYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USANYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
机构:
Harvard Univ, Sch Med, Div Cellular & Mol Physiol, Joslin Diabet Ctr, Boston, MA 02250 USAHarvard Univ, Sch Med, Div Cellular & Mol Physiol, Joslin Diabet Ctr, Boston, MA 02250 USA
Abedini, Andisheh
;
Raleigh, Daniel P.
论文数: 0引用数: 0
h-index: 0
机构:
SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USA
SUNY Stony Brook, Grad Program Biophys, Grad Program Biochem & Struct Biol, Stony Brook, NY 11794 USAHarvard Univ, Sch Med, Div Cellular & Mol Physiol, Joslin Diabet Ctr, Boston, MA 02250 USA
机构:
Virginia Polytech Inst & State Univ, Dept Biochem, Blacksburg, VA 24061 USAVirginia Polytech Inst & State Univ, Dept Biochem, Blacksburg, VA 24061 USA
Allen, William J.
;
Lemkul, Justin A.
论文数: 0引用数: 0
h-index: 0
机构:
Virginia Polytech Inst & State Univ, Dept Biochem, Blacksburg, VA 24061 USAVirginia Polytech Inst & State Univ, Dept Biochem, Blacksburg, VA 24061 USA
Lemkul, Justin A.
;
Bevan, David R.
论文数: 0引用数: 0
h-index: 0
机构:
Virginia Polytech Inst & State Univ, Dept Biochem, Blacksburg, VA 24061 USAVirginia Polytech Inst & State Univ, Dept Biochem, Blacksburg, VA 24061 USA
机构:
Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USAUniv So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA
Apostolidou, Melania
;
Jayasinghe, Sajith A.
论文数: 0引用数: 0
h-index: 0
机构:
Calif State Univ, Dept Chem & Biochem, San Marcos, CA 92096 USAUniv So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA
Jayasinghe, Sajith A.
;
Langen, Ralf
论文数: 0引用数: 0
h-index: 0
机构:
Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USAUniv So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA
机构:
NYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USANYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Abedini, Andisheh
;
Plesner, Annette
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Pathol & Lab Med, Child & Family Res Inst, Vancouver, BC, Canada
Univ British Columbia, Dept Surg, Vancouver, BC, Canada
Novo Nordisk AS, Bagsvaerd, DenmarkNYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Plesner, Annette
;
Cao, Ping
论文数: 0引用数: 0
h-index: 0
机构:
SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USANYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Cao, Ping
;
Ridgway, Zachary
论文数: 0引用数: 0
h-index: 0
机构:
SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USANYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Ridgway, Zachary
;
Zhang, Jinghua
论文数: 0引用数: 0
h-index: 0
机构:
NYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USANYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Zhang, Jinghua
;
Tu, Ling-Hsien
论文数: 0引用数: 0
h-index: 0
机构:
SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USANYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Tu, Ling-Hsien
;
Middleton, Chris T.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Wisconsin, Dept Chem, Madison, WI 53706 USA
Phase Tech Spect Inc, Madison, WI USANYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Middleton, Chris T.
;
Chao, Brian
论文数: 0引用数: 0
h-index: 0
机构:
NYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USANYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Chao, Brian
;
Sartori, Daniel J.
论文数: 0引用数: 0
h-index: 0
机构:
NYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USANYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Sartori, Daniel J.
;
Meng, Fanling
论文数: 0引用数: 0
h-index: 0
机构:
SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USANYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Meng, Fanling
;
Wang, Hui
论文数: 0引用数: 0
h-index: 0
机构:
SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USANYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Wang, Hui
;
Wong, Amy G.
论文数: 0引用数: 0
h-index: 0
机构:
SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USANYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Wong, Amy G.
;
Zanni, Martin T.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Wisconsin, Dept Chem, Madison, WI 53706 USANYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Zanni, Martin T.
;
Verchere, C. Bruce
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Pathol & Lab Med, Child & Family Res Inst, Vancouver, BC, Canada
Univ British Columbia, Dept Surg, Vancouver, BC, CanadaNYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Verchere, C. Bruce
;
Raleigh, Daniel P.
论文数: 0引用数: 0
h-index: 0
机构:
SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USANYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
Raleigh, Daniel P.
;
Schmidt, Ann Marie
论文数: 0引用数: 0
h-index: 0
机构:
NYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USANYU, Sch Med, Dept Med, Diabetes Res Program,Div Endocrinol Diabet & Meta, New York, NY 10003 USA
机构:
Harvard Univ, Sch Med, Div Cellular & Mol Physiol, Joslin Diabet Ctr, Boston, MA 02250 USAHarvard Univ, Sch Med, Div Cellular & Mol Physiol, Joslin Diabet Ctr, Boston, MA 02250 USA
Abedini, Andisheh
;
Raleigh, Daniel P.
论文数: 0引用数: 0
h-index: 0
机构:
SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USA
SUNY Stony Brook, Grad Program Biophys, Grad Program Biochem & Struct Biol, Stony Brook, NY 11794 USAHarvard Univ, Sch Med, Div Cellular & Mol Physiol, Joslin Diabet Ctr, Boston, MA 02250 USA
机构:
Virginia Polytech Inst & State Univ, Dept Biochem, Blacksburg, VA 24061 USAVirginia Polytech Inst & State Univ, Dept Biochem, Blacksburg, VA 24061 USA
Allen, William J.
;
Lemkul, Justin A.
论文数: 0引用数: 0
h-index: 0
机构:
Virginia Polytech Inst & State Univ, Dept Biochem, Blacksburg, VA 24061 USAVirginia Polytech Inst & State Univ, Dept Biochem, Blacksburg, VA 24061 USA
Lemkul, Justin A.
;
Bevan, David R.
论文数: 0引用数: 0
h-index: 0
机构:
Virginia Polytech Inst & State Univ, Dept Biochem, Blacksburg, VA 24061 USAVirginia Polytech Inst & State Univ, Dept Biochem, Blacksburg, VA 24061 USA
机构:
Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USAUniv So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA
Apostolidou, Melania
;
Jayasinghe, Sajith A.
论文数: 0引用数: 0
h-index: 0
机构:
Calif State Univ, Dept Chem & Biochem, San Marcos, CA 92096 USAUniv So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA
Jayasinghe, Sajith A.
;
Langen, Ralf
论文数: 0引用数: 0
h-index: 0
机构:
Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USAUniv So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA