Journal of Chemical Information and Modeling,
Journal Year:
2024,
Volume and Issue:
64(17), P. 6857 - 6865
Published: Aug. 27, 2024
As
a
critical
sensor
protein,
NLRP3
detects
cellular
perturbation
caused
by
diverse
exogenous
and
endogenous
stimuli.
activation
requires
domain
rotation
within
the
NEK7-bound
monomer
assembly.
However,
detailed
molecular
mechanism
for
assembly
remains
elusive,
particularly
in
terms
of
dynamics
energetics.
In
this
work,
all-atom
(MD)
simulations
are
executed
to
describe
large-amplitude
closed-to-open
conformational
transitions
along
rotational
pathway.
From
MD
trajectories,
computed
potential
mean
force
(PMF)
shows
that
through
monomeric
is
an
uphill
process,
during
which
active
conformation
NLRP3-NEK7
cannot
be
stabilized.
Further
binding
free-energy
calculations
two
neighboring
subunits
disc
with
C10
symmetry
reveal
protein
self-assembly
starts
approximately
at
86.5°
position
on
rotary
pathway,
becomes
downhill
process
state
90.5°.
The
stabilized
because
interactions
between
subunits,
involving
mainly
FISNA
loop
1
one
subunit
"crocodile-clip"
structure
formed
NBD
helix-loop-strand
motif
(residues
351-373)
WHD
β-hairpin
501-521)
other.
Our
also
demonstrate
NEK7
plays
important
role
cage
dissociation
centrosome,
consistent
biological
experiments.
computational
results
provide
kinetic,
energetic,
structural
insights
into
mechanisms
NEK7-driven
inactive
cages.
proposed
work
significantly
different
from
those
previous
studies.
Comorbid
anxiety
in
chronic
pain
is
clinically
common,
with
a
comorbidity
rate
of
over
50%.
The
main
treatments
are
based
on
pharmacological,
interventional,
and
implantable
approaches,
which
have
limited
efficacy
carry
risk
side
effects.
Here,
we
report
terahertz
(THz,
10
12
Hz)
wave
stimulation
(THS)
technique,
exerts
nonthermal,
long-term
modulatory
effects
neuronal
activity
by
reducing
the
binding
between
nano-sized
glutamate
molecules
GluA2,
leading
to
relief
comorbid
anxiety-like
behaviors
mice.
In
mice
co-occurring
induced
complete
Freund’s
adjuvant
(CFA)
injection,
hyperactivity
was
observed
glutamatergic
neurons
anterior
cingulate
cortex
(ACC
Glu
).
Using
whole-cell
recording
ACC
slices,
demonstrated
that
THS
(34
THz)
effectively
inhibited
excitability
.
Moreover,
molecular
dynamics
simulations
showed
reduced
number
hydrogen
bonds
bound
GluA2.
Furthermore,
target
CFA-treatment
suppressed
and,
as
result,
alleviated
behaviors.
Consistently,
inhibition
chemogenetics
mimics
THS-induced
antinociceptive
antianxiety
behavior.
Together,
our
study
provides
evidence
for
an
intervention
technique
modulating
viable
clinical
treatment
strategy
anxiety.
Frontiers in Plant Science,
Journal Year:
2024,
Volume and Issue:
15
Published: April 8, 2024
Bulbil
is
an
important
asexual
reproductive
structure
of
bulbil
plants.
It
mainly
grows
in
leaf
axils,
forks,
tubers
and
the
upper
near
ground
ends
flower
stems
They
play
a
significant
role
reproduction
numerous
herbaceous
plant
species
by
serving
as
agents
propagation,
energy
reserves,
survival
mechanisms
adverse
environmental
conditions.
Despite
extensive
research
on
bulbil-plants
regarding
their
resources,
development
mechanisms,
utilisation,
comprehensive
review
lacking,
hindering
progress
exploiting
resources.
This
paper
provides
systematic
overview
research,
including
bulbil-plant
identification
stages
maturity
bulbils,
cellular
molecular
development,
factors
influencing
gene
related
to
multi-bulbil
phenomenon
its
significance,
medicinal
value
breeding
application
tissue
culture
technology
production.
The
Temporary
Immersion
Bioreactor
System
(TIBS)
Terahertz
(THz)
also
discussed,
offering
blueprint
for
further
resource
development.
Additionally,
additive,
seven
areas
that
require
attention
are
proposed:
(1)
Utilization
modern
network
technologies,
such
recognition
apps
or
websites,
collect
identify
bulbous
resources
efficiently
extensively;
(2)
Further
cell
structures
influence
bulb
development;
(3)
Investigation
regulatory
relationship
between
genes,
proteins,
metabolites,
epigenetics
(4)
Exploration
potential
utilization
multiple
sprouts,
medicinal,
ecological,
horticultural
applications;
(5)
Innovation
optimization
system
bulbils;
(6)
Comprehensive
TIBS
large-scale
expansion
production;
(7)
To
find
out
common
share
genetics
bulbils
flowers.
The Journal of Physical Chemistry B,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Sept. 27, 2024
The
binding
of
nicotine
(NCT)
to
acetylcholine-binding
protein
(AChBP)
plays
an
important
role
in
synaptic
transmission
and
neurotransmitter
regulation.
However,
effectively
regulating
their
or
dissociation
processes
remains
a
challenging
problem.
In
this
study,
we
employed
all-atom
molecular
dynamics
(MD)
simulations
systematically
investigate
the
impact
external
terahertz
(THz)
waves
on
kinetics
between
AChBP
NCT.
We
first
identified
key
residues
(i.e.,
W143)
interactions
hydrogen
bonding
cation-π
interaction)
AChBP-NCT
without
THz
waves.
then
investigated
charged
NCT
with
at
three
different
frequencies
13.02,
21.44,
42.55
THz).
Importantly,
predominant
vibrational
modes
13.02
can
drive
rotation
pentagonal
ring
This
leads
disruption
bonds
W143
reduced
likelihood
forming
interactions,
resulting
from
AChBP.
Additionally,
further
influence
electric
field
intensities
found
that
when
intensity
exceeds
critical
value
(∼0.60
V/nm),
probability
ligand
gradually
rises
as
increases.
general,
study
contributes
better
understanding
effects
protein-ligand
which
might
also
shed
some
light
potential
applications
addiction
treatment
therapeutic
strategies
for
neurodegenerative
diseases.
Journal of the American Chemical Society,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 8, 2025
Our
recent
molecular
dynamics
simulations
of
decomposing
Alzheimer's
disease
plaques,
under
oscillating-
and
static
external
electric
fields
(Os-EEFs
St-EEFs),
revealed
the
superiority
Os-EEF
for
plaques
consisting
7-residue
peptide
segment.
This
conclusion
is
now
reinforced
by
studying
dimers
short
peptides
trimers
full-length
Aβ-42
peptide.
Thus,
dispersed
obtained
following
St-EEF
applications
reformed
once
subsided.
In
contrast,
originating
from
application
remained
long
time
scales.
The
present
study
provides
insights
into
these
results
modeling
decomposition
modes
that
transpire
both
field
types.
Additionally,
this
frequency
effects
on
processes
within
THz–MHz
regions.
simulation
shows
in
lower
range
(≤GHz)
decomposes
plaque
a
scale
∼50
ns,
whereas
higher
Os-EEFs
(≥THz)
are
less
effective.
As
such,
with
moderate-to-low
frequencies
lead
to
an
"explosion,"
whereby
fly
distantly
apart
inhibit
reformation.
By
St-EEFs
form
parallel
pairs,
which
stabilized
EEF
due
large
dipole
moment
ensemble.
sluggish
reversible
processes.
We
further
conclude
impact
maximal
pulses,
prevents
propensity
arrange
pairs.
over
maintained
irrespective
peptides'
length.
A
model
formulated
predicts
dependence
EEF.
Cell Reports Physical Science,
Journal Year:
2025,
Volume and Issue:
6(2), P. 102436 - 102436
Published: Feb. 1, 2025
Highlights•Membrane
association
of
Aβ40
initiates
multiple
pathways,
leading
to
polymorphism•Membranes
facilely
stabilize
small
oligomeric
seeds•Key
residues
facilitate
an
ordered
release
seeds
from
membranes•Polymorphic
fibrils
may
share
structural
motifs
and
be
related
by
domain
swapSummaryAlzheimer's
disease
(AD)
is
caused
the
assembly
amyloid-beta
(Aβ)
peptides
into
oligomers
fibrils.
Endogenous
Aβ
aggregation
assisted
cell
membranes,
which
can
accelerate
nucleation
step
enormously,
but
knowledge
membrane-assisted
still
very
limited.
Here,
we
used
extensive
molecular
dynamics
(MD)
simulations
structurally
energetically
characterize
key
intermediates
along
pathways
Aβ40.
Reinforcing
experimental
observations,
reveal
unique
roles
GM1
ganglioside
cholesterol
in
stabilizing
membrane-embedded
β
sheets
Y10
K28
a
seed
solution.
The
same
leads
either
open-shaped
or
R-shaped
fibril,
with
significant
stabilization
provided
inter-
intra-subunit
interfaces
between
straight
sheet
(residues
Q15–D23)
bent
A30–V36).
This
work
presents
comprehensive
picture
Aβ40,
broad
implications
for
developing
AD
therapies
rationalizing
disease-specific
polymorphisms
amyloidogenic
proteins.Graphical
abstract
The Journal of Chemical Physics,
Journal Year:
2025,
Volume and Issue:
162(18)
Published: May 8, 2025
Transient
receptor
potential
vanilloid
1
(TRPV1)
is
a
critical
non-selective
cation
channel
involved
in
various
biological
and
physiological
processes,
making
it
promising
drug
target
for
treating
multiple
diseases.
Capsaicin,
TRPV1
agonist,
widely
used
to
relieve
pain
by
desensitizing
the
with
persistent
stimulation.
However,
initially
intolerable
burning
sensation
due
activation
necessitates
use
of
antagonists
deactivate
mitigate
discomfort,
which
yet
causes
thermoregulation
disorders.
In
this
study,
molecular
dynamics
simulations
reveal
that
frequency-specific
terahertz
(THz)
waves
can
promote
capsaicin
unbinding
from
TRPV1,
suggesting
spatiotemporally
controlled
approach
deactivation.
The
THz
wave
resonates
hydroxyl
group
head,
increasing
its
rotational
kinetic
energy
promoting
rotation.
This
disrupts
key
hydrogen
bond
between
residue
E570,
significantly
reducing
capsaicin’s
affinity
TRPV1.
Our
findings
suggest
could
mimic
more
flexible
way,
offering
temporal
control
over
recruitment
expulsion
(i.e.,
activation,
desensitization,
deactivation)
comfortable
relief.
addition,
work
enlightens
THz-based,
pill-free
strategy
induced
inflammatory
ligands
activated
Physical Chemistry Chemical Physics,
Journal Year:
2024,
Volume and Issue:
26(34), P. 22413 - 22422
Published: Jan. 1, 2024
Using
molecular
dynamics,
we
studied
the
impact
of
THz
waves
on
choline
binding
to
acetyltransferase
and
found
that
specific
frequencies
can
influence
this
binding,
potentially
affecting
acetylcholine
synthesis.