A brief history of amyloid aggregation simulations
Wiley Interdisciplinary Reviews Computational Molecular Science,
Год журнала:
2024,
Номер
14(1)
Опубликована: Янв. 1, 2024
Abstract
Amyloid
proteins
are
characterized
by
their
tendency
to
aggregate
into
amyloid
fibrils,
which
often
associated
with
devastating
diseases.
Aggregation
pathways
typically
involve
unfolding
or
misfolding
of
monomeric
and
formation
transient
oligomers
protofibrils
before
the
final
aggregation
product
is
formed.
The
conformational
dynamics
polymorphic
volatile
nature
these
intermediates
make
characterization
experimental
techniques
alone
insufficient
also
require
computational
approaches.
Over
past
25
years,
size
simulated
systems
length
simulations
have
increased
significantly.
These
advances
discussed
here.
review
includes
simulation
approaches
that
model
aggregating
peptides
at
both
all‐atom
coarse‐grained
levels,
use
molecular
Monte
Carlo
sampling
simulate
changes,
present
results
for
various
ranging
from
Lys‐Phe‐Phe‐Glu
(KFFE)
as
smallest
system
an
intermediate‐sized
peptide
α‐synuclein.
presentation
history
concludes
a
discussion
where
future
may
lie.
This
article
categorized
under:
Structure
Mechanism
>
Computational
Biochemistry
Biophysics
Molecular
Statistical
Mechanics
Dynamics
Monte‐Carlo
Methods
Язык: Английский
Peptide Self-Assembly into Amyloid Fibrils: Unbiased All-Atom Simulations
The Journal of Physical Chemistry B,
Год журнала:
2024,
Номер
128(14), С. 3320 - 3328
Опубликована: Март 6, 2024
Protein
self-assembly
plays
an
important
role
in
biological
systems,
accounting
for
the
formation
of
mesoscopic
structures
that
can
be
highly
symmetric
as
capsid
viruses
or
disordered
molecular
condensates
exhibit
a
one-dimensional
fibrillar
morphology
amyloid
fibrils.
Deposits
latter
tissues
individuals
with
degenerative
diseases
like
Alzheimer's
and
Parkinson's
has
motivated
extensive
efforts
to
understand
sequence
events
their
formation.
These
studies
aim
identify
on-pathway
intermediates
may
targets
therapeutic
intervention.
This
detailed
knowledge
fibril
remains
obscure,
part
due
challenges
experimental
analyses
these
processes.
However,
progress
is
being
achieved
short
peptides
advances
our
ability
perform
completely
unbiased
all-atom
simulations
process.
perspective
discusses
recent
developments,
implications,
hurdles
still
need
overcome
further
advance
field.
Язык: Английский
Impact of Amidation on Aβ25–35 Aggregation
The Journal of Physical Chemistry B,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 13, 2025
Toxic
oligomeric
species
are
suspected
in
the
etiology
of
Alzheimer's
disease.
The
full-length
Aβ42
can
be
studied
by
fragment
Aβ25-35
as
it
retains
neurotoxicity.
According
to
experimental
studies,
amidation
carboxyl
terminal
decreases
fibrillation
activity
while
retaining
its
neurotoxic
properties.
Our
molecular
dynamics
simulation
aggregation
trimer
from
two
initial
structures
(fibril
and
randomized
helical
structures)
their
amidated
nonamidated
forms.
Comparing
systems,
results
suggest
that
antiparallel
chains
dominant
amide
group
leads
parallel
chains.
In
terms
secondary
structures,
a
higher
helix
content
with
corresponding
decrease
β-sheet
is
observed
consequence
amidation.
Despite
variation
chain-chain
contacts
still
mediated
Gly
motif
(GxxxG)
Ile
residues
both
systems.
As
neurotoxicity
does
not
change
upon
amidation,
our
imply
clumping
peptides
sustained
greater
contributing
factor
toxicity
than
quaternary
structures.
Язык: Английский
Multistep molecular mechanisms of Aβ16-22 fibril formation revealed by lattice Monte Carlo simulations
The Journal of Chemical Physics,
Год журнала:
2023,
Номер
158(23)
Опубликована: Июнь 15, 2023
As
a
model
of
self-assembly
from
disordered
monomers
to
fibrils,
the
amyloid-β
fragment
Aβ16-22
was
subject
past
numerous
experimental
and
computational
studies.
Because
dynamics
information
between
milliseconds
seconds
cannot
be
assessed
by
both
studies,
we
lack
full
understanding
its
oligomerization.
Lattice
simulations
are
particularly
well
suited
capture
pathways
fibrils.
In
this
study,
explored
aggregation
10
peptides
using
65
lattice
Monte
Carlo
simulations,
each
simulation
consisting
3
×
109
steps.
Based
on
total
24
41
that
converge
do
not
fibril
state,
respectively,
able
reveal
diversity
leading
structure
conformational
traps
slowing
down
formation.
Язык: Английский