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@ARTICLE{Illig:889720,
author = {Illig, Alexander-Maurice and Strodel, Birgit},
title = {{P}erformance of {M}arkov {S}tate {M}odels and {T}ransition
{N}etworks on {C}haracterizing {A}myloid {A}ggregation
{P}athways from {MD} {D}ata},
journal = {Journal of chemical theory and computation},
volume = {16},
number = {12},
issn = {1549-9626},
address = {Washington, DC},
reportid = {FZJ-2021-00342},
pages = {7825 - 7839},
year = {2020},
abstract = {Molecular dynamic (MD) simulations are animportant tool for
studying protein aggregation processes, whichplay a central
role in a number of diseases including Alzheimer’sdisease.
However, MD simulations produce large amounts of
data,requiring advanced methods to extract mechanistic
insight into theprocess under study. Transition networks
(TNs) provide anelegant method to identify (meta)stable
states and the transitionsbetween them from MD simulations.
Here, we apply two differentmethods to generate TNs for
protein aggregation: Markov statemodels (MSMs), which are
based on kinetic clustering the statespace, and TNs using
conformational clustering. The similaritiesand differences
of both methods are elucidated for the aggregationof the
fragment Aβ16−22 of the Alzheimer’s amyloid-β peptide.
Ingeneral, both methods perform excellently in identifying
the main aggregation pathways. The strength of MSMs is that
they providea rather coarse and thus simply to interpret
picture of the aggregation process. Conformation-sorting
TNs, on the other hand,outperform MSMs in uncovering
mechanistic details. We thus recommend to apply both methods
to MD data of proteinaggregation in order to obtain a
complete picture of this process. As part of this work, a
Python script called ATRANET forautomated TN generation
based on a correlation analysis of the descriptors used for
conformational sorting is made publiclyavailable.},
cin = {IBI-7},
ddc = {610},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {553 - Physical Basis of Diseases (POF3-553)},
pid = {G:(DE-HGF)POF3-553},
typ = {PUB:(DE-HGF)16},
pubmed = {33233894},
UT = {WOS:000598208600044},
doi = {10.1021/acs.jctc.0c00727},
url = {https://juser.fz-juelich.de/record/889720},
}