2016
DOI: 10.1007/978-1-4939-2978-8_16
|View full text |Cite
|
Sign up to set email alerts
|

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

Abstract: 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 th… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
4
1

Citation Types

0
5
0

Year Published

2019
2019
2021
2021

Publication Types

Select...
4
1

Relationship

0
5

Authors

Journals

citations
Cited by 5 publications
(5 citation statements)
references
References 90 publications
0
5
0
Order By: Relevance
“…These include: (i) the self-assembly and deposition of multiple types of fibrillar and globular structures and polymorphic assemblies both in solution and on membrane surfaces; and (ii) the formation of heterogeneous ionic pores spanning the lipid bilayer that is linked to the pathogenicity of these molecules. These later findings are supported by multiple independent reports regarding the capability of Aβ42 peptides [2 hydrophobic amino acid residues (isoleucine and alanine) longer (at the C-terminal) than Aβ40] to form up to 2.4-nm diameter pores through lipid bilayer membranes (Lashuel et al, 2002; Connelly et al, 2012; Sciacca et al, 2012; Ullah et al, 2015; Di Scala et al, 2016; Jang et al, 2016; Davidson, 2019; Hicks et al, 2019; Nguyen et al, 2019; Sun et al, 2019; Österlund et al, 2019). Interestingly, the slightly longer and more hydrophobic Aβ42-based peptide assemblies in oligomeric preparations have been observed to form voltage-independent, non-selective ion channels in contrast to Aβ40 peptide-based oligomers, fibers, and monomers which do not generally support pore structure formation (Bode et al, 2017, 2019; Nguyen et al, 2019).…”
Section: Aβ42 Peptides and Lps In Ad Neuronsmentioning
confidence: 53%
“…These include: (i) the self-assembly and deposition of multiple types of fibrillar and globular structures and polymorphic assemblies both in solution and on membrane surfaces; and (ii) the formation of heterogeneous ionic pores spanning the lipid bilayer that is linked to the pathogenicity of these molecules. These later findings are supported by multiple independent reports regarding the capability of Aβ42 peptides [2 hydrophobic amino acid residues (isoleucine and alanine) longer (at the C-terminal) than Aβ40] to form up to 2.4-nm diameter pores through lipid bilayer membranes (Lashuel et al, 2002; Connelly et al, 2012; Sciacca et al, 2012; Ullah et al, 2015; Di Scala et al, 2016; Jang et al, 2016; Davidson, 2019; Hicks et al, 2019; Nguyen et al, 2019; Sun et al, 2019; Österlund et al, 2019). Interestingly, the slightly longer and more hydrophobic Aβ42-based peptide assemblies in oligomeric preparations have been observed to form voltage-independent, non-selective ion channels in contrast to Aβ40 peptide-based oligomers, fibers, and monomers which do not generally support pore structure formation (Bode et al, 2017, 2019; Nguyen et al, 2019).…”
Section: Aβ42 Peptides and Lps In Ad Neuronsmentioning
confidence: 53%
“…Furthermore, the results of Pacheco et al ( 2015 ) go in line with the data of β-amyloid, another experimentally confirmed amyloidogenic pore forming peptide (Sepúlveda et al, 2014 ). Models of rather mobile Aβ channels have been proposed already in 2007 by the Nussinov group, who used molecular dynamics simulations (Jang et al, 2007 , 2009 , 2016 ; Capone et al, 2012 ). The simulations indicated that β-sheet channels might break into loosely associated mobile β-sheet subunits.…”
Section: Introductionmentioning
confidence: 99%
“…Whereas structure-based protein design approaches have shown notable successes in several cases, their application to de novo β-sheet designs still remains a challenge. , Although structure-based design approaches require a well-defined protein structure, amyloidogenic peptides usually have highly disordered structures . The structural identification of such peptides has long been hindered by high degrees of structural plasticity, transiency, and complexity owing to a self-oligomerization. , It is thus necessary to exploit the complementarity across neighboring β-strand pairs using sequence information.…”
Section: Introductionmentioning
confidence: 99%
“…2,10 Although structure-based design approaches require a well-defined protein structure, amyloidogenic peptides usually have highly disordered structures. 11 The structural identification of such peptides has long been hindered by high degrees of structural plasticity, transiency, and complexity owing to a self-oligomerization. 12,13 It is thus necessary to exploit the complementarity across neighboring β-strand pairs using sequence information.…”
Section: ■ Introductionmentioning
confidence: 99%