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@ARTICLE{Sengupta:872771,
author = {Sengupta, Ushnish and Carballo-Pacheco, Martín and
Strodel, Birgit},
title = {{A}utomated {M}arkov state models for molecular dynamics
simulations of aggregation and self-assembly},
journal = {The journal of chemical physics},
volume = {150},
number = {11},
issn = {1089-7690},
address = {Melville, NY},
publisher = {American Institute of Physics},
reportid = {FZJ-2020-00249},
pages = {115101 -},
year = {2019},
abstract = {Markov state models have become popular in the
computational biochemistry and biophysics communities as a
technique for identifying stationary and kinetic information
of protein dynamics from molecular dynamics simulation data.
In this paper, we extend the applicability of automated
Markov state modeling to simulation data of molecular
self-assembly and aggregation by constructing collective
coordinates from molecular descriptors that are invariant to
permutations of molecular indexing. Understanding molecular
self-assembly is of critical importance if we want to deepen
our understanding of neurodegenerative diseases where the
aggregation of misfolded or disordered proteins is thought
to be the main culprit. As a proof of principle, we
demonstrate our Markov state model technique on simulations
of the KFFE peptide, a subsequence of Alzheimer’s
amyloid-β peptide and one of the smallest peptides known to
aggregate into amyloid fibrils in vitro. We investigate the
different stages of aggregation up to tetramerization and
show that the Markov state models clearly map out the
different aggregation pathways. Of note is that disordered
and β-sheet oligomers do not interconvert, leading to
separate pathways for their formation. This suggests that
amyloid aggregation of KFFE occurs via ordered aggregates
from the very beginning. The code developed here is freely
available as a Jupyter notebook called TICAgg, which can be
used for the automated analysis of any self-assembling
molecular system, protein, or otherwise},
cin = {ICS-6 / JARA-HPC},
ddc = {530},
cid = {I:(DE-Juel1)ICS-6-20110106 / $I:(DE-82)080012_20140620$},
pnm = {553 - Physical Basis of Diseases (POF3-553) / Aggregation
of Functional Amyloids $(jara0095_20140501)$},
pid = {G:(DE-HGF)POF3-553 / $G:(DE-Juel1)jara0095_20140501$},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30901988},
UT = {WOS:000462014500035},
doi = {10.1063/1.5083915},
url = {https://juser.fz-juelich.de/record/872771},
}