Computational Methods for Structural and Functional Studies of Alzheimer’s Amyloid Ion Channels

  • Hyunbum Jang
  • Fernando Teran Arce
  • Joon Lee
  • Alan L. Gillman
  • Srinivasan Ramachandran
  • Bruce L. Kagan
  • Ratnesh Lal
  • Ruth NussinovEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1345)


Aggregation can be studied by a range of methods, experimental and computational. Aggregates form in solution, across solid surfaces, and on and in the membrane, where they may assemble into unregulated leaking ion channels. Experimental probes of ion channel conformations and dynamics are challenging. Atomistic molecular dynamics (MD) simulations are capable of providing insight into structural details of amyloid ion channels in the membrane at a resolution not achievable experimentally. Since data suggest that late stage Alzheimer’s disease involves formation of toxic ion channels, MD simulations have been used aiming to gain insight into the channel shapes, morphologies, pore dimensions, conformational heterogeneity, and activity. These can be exploited for drug discovery. Here we describe computational methods to model amyloid ion channels containing the β-sheet motif at atomic scale and to calculate toxic pore activity in the membrane.

Key words

Amyloid channel β-Sheet channel Lipid bilayer Molecular dynamics simulations CHARMM NAMD 



This project has been funded in whole or in part with Federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health, under contract HHSN261200800001E. This research was supported [in part] by the Intramural Research Program of NIH, Frederick National Lab, Center for Cancer Research. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Hyunbum Jang
    • 1
  • Fernando Teran Arce
    • 2
    • 3
  • Joon Lee
    • 3
  • Alan L. Gillman
    • 2
  • Srinivasan Ramachandran
    • 2
    • 3
  • Bruce L. Kagan
    • 4
  • Ratnesh Lal
    • 2
    • 3
  • Ruth Nussinov
    • 1
    • 5
    Email author
  1. 1.Cancer and Inflammation Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer ResearchNational Cancer Institute at FrederickFrederickUSA
  2. 2.Department of Bioengineering, Materials Science ProgramUniversity of California, San DiegoLa JollaUSA
  3. 3.Department of Mechanical and Aerospace Engineering, Materials Science ProgramUniversity of California, San DiegoLa JollaUSA
  4. 4.Department of Psychiatry, David Geffen School of Medicine, Semel Institute for Neuroscience and Human BehaviorUniversity of CaliforniaLos AngelesUSA
  5. 5.Department of Human Molecular Genetics and Biochemistry, Sackler School of MedicineTel Aviv UniversityTel AvivIsrael

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