Molecular dynamics simulations are used to provide insights into the molecular mechanisms accounting for binding of amyloid fibrils to lipid bilayers and to study the effect of cholesterol in this process. We show that electrostatic interactions play an important role in fibril-bilayer binding and cholesterol modulates this interaction. In particular, the interaction between positive residues and lipid head groups becomes more favorable in the presence of cholesterol. Consistent with experiments, we find that cholesterol enhances fibril-membrane binding.
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Kobe Univ, Grad Sch Med, Chuo Ku, Div Struct Biol,Dept Biochem & Mol Biol, Kobe, Hyogo 6500017, JapanKobe Univ, Grad Sch Med, Chuo Ku, Div Struct Biol,Dept Biochem & Mol Biol, Kobe, Hyogo 6500017, Japan
Sasahara, Kenji
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Hall, Damien
Hamada, Daizo
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Kobe Univ, Grad Sch Med, Chuo Ku, Div Struct Biol,Dept Biochem & Mol Biol, Kobe, Hyogo 6500017, JapanKobe Univ, Grad Sch Med, Chuo Ku, Div Struct Biol,Dept Biochem & Mol Biol, Kobe, Hyogo 6500017, Japan
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Weill Cornell Med Coll, Triinst Program Computat Biol & Med, New York, NY USA
Cornell Univ, Ithaca, NY USAWeill Cornell Med Coll, Triinst Program Computat Biol & Med, New York, NY USA
Doktorova, Milka
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Dick, Robert
Heberle, Frederick A.
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Oak Ridge Natl Lab, Biol & Soft Matter Div, Oak Ridge, TN USA
Univ Tennessee, Bredesen Ctr Interdisciplinary Res & Grad Educ, Knoxville, TN USAWeill Cornell Med Coll, Triinst Program Computat Biol & Med, New York, NY USA
Heberle, Frederick A.
Feigenson, Gerald W.
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Cornell Univ, Ithaca, NY USAWeill Cornell Med Coll, Triinst Program Computat Biol & Med, New York, NY USA
Feigenson, Gerald W.
Vogt, Volker M.
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Cornell Univ, Ithaca, NY USAWeill Cornell Med Coll, Triinst Program Computat Biol & Med, New York, NY USA