Kinases and Phosphatases,
Journal Year:
2024,
Volume and Issue:
2(1), P. 43 - 66
Published: Jan. 31, 2024
Protein
kinase
CK2
(CK2)
influences
one-fifth
of
the
cellular
phosphoproteome.
It
regulates
almost
all
pathways
and
is
thus
a
critical
switch
between
biological
processes
within
cell.
Inhibition
reverses
oncogene
addiction
tumor
alters
microenvironment.
The
success
this
strategy
its
clinical
translation
opens
new
opportunities.
Targeting
in
musculoskeletal
disorders
promising.
Clinical
manifestations
these
include
dysfunctional
inflammation,
dysregulated
cell
differentiation,
senescence.
Processes
regulated
by
these.
Its
emerging
role
senescence
also
indicates
function’s
centrality
metabolism.
This
review
summarizes
considerations
for
targeting
disorders.
We
have
discussed
implications
CK2-regulated
Abstract
Biological
membranes
(biomembranes)
are
one
of
the
most
complicated
structures
that
allow
life
to
exist.
Investigating
their
structure,
dynamics,
and
function
is
crucial
for
advancing
our
knowledge
cellular
mechanisms
developing
novel
therapeutic
strategies.
However,
experimental
investigation
many
biomembrane
phenomena
challenging
due
compositional
structural
complexity,
as
well
inherently
multi‐scalar
features.
Computational
approaches,
particularly
molecular
dynamics
(MD)
simulations,
have
emerged
powerful
tools
addressing
atomic
details
systems,
driving
breakthroughs
in
understanding
biomembranes
roles
function.
This
review
presents
an
overview
latest
advancements
related
computational
from
force
fields
model
construction
MD
simulations
trajectory
analysis.
We
also
discussed
current
hot
research
topics
challenges.
Finally,
we
outline
future
directions,
emphasizing
integration
field
development,
enhanced
sampling
techniques,
data‐driven
approaches
accelerate
growth
this
years
come.
aim
equip
readers
with
promise
limitations
emerging
technologies
systems
offer
valuable
recommendations
endeavors.
article
categorized
under:
Structure
Mechanism
>
Biochemistry
Biophysics
Molecular
Statistical
Mechanics
Dynamics
Monte‐Carlo
Methods
Briefings in Bioinformatics,
Journal Year:
2023,
Volume and Issue:
24(6)
Published: Sept. 22, 2023
Abstract
Blood-brain
barrier
penetrating
peptides
(BBBPs)
are
short
peptide
sequences
that
possess
the
ability
to
traverse
selective
blood-brain
interface,
making
them
valuable
drug
candidates
or
carriers
for
various
payloads.
However,
in
vivo
vitro
validation
of
BBBPs
is
resource-intensive
and
time-consuming,
driving
need
accurate
silico
prediction
methods.
Unfortunately,
scarcity
experimentally
validated
hinders
efficacy
current
machine-learning
approaches
generating
reliable
predictions.
In
this
paper,
we
present
DeepB3P3,
a
novel
framework
prediction.
Our
contribution
encompasses
four
key
aspects.
Firstly,
propose
deep
learning
model
consisting
transformer
encoder
layer,
convolutional
network
backbone,
capsule
classification
head.
This
integrated
architecture
effectively
learns
representative
features
from
sequences.
Secondly,
introduce
masked
as
powerful
data
augmentation
technique
compensate
small
training
set
sizes
BBBP
Thirdly,
develop
threshold-tuning
method
handle
imbalanced
by
approximating
optimal
decision
threshold
using
set.
Lastly,
DeepB3P3
provides
an
estimation
uncertainty
level
associated
with
each
Through
extensive
experiments,
demonstrate
achieves
state-of-the-art
accuracy
up
98.31%
on
benchmarking
dataset,
solidifying
its
potential
promising
computational
tool
discovery
BBBPs.
Biomedicine & Pharmacotherapy,
Journal Year:
2024,
Volume and Issue:
174, P. 116610 - 116610
Published: April 19, 2024
Depression
ranks
as
the
fourth
most
prevalent
global
disease,
with
suicide
incidents
occurring
at
a
younger
age.
Sulpiride
(SUL),
an
atypical
antidepressant
drug
acting
dopamine
D2
receptor
antagonist
and
possessing
anti-inflammatory
properties,
exhibits
limited
ability
to
penetrate
blood
brain
barrier
(BBB).
This
weak
penetration
hampers
its
inhibitory
effect
on
prolactin
release
in
pituitary
gland,
consequently
leading
hyperprolactinemia.
In
order
enhance
central
nervous
system
efficacy
of
sulpiride
reduce
serum
levels,
we
covalently
linked
VPALR
derived
from
nuclear
DNA
repair
protein
ku70.
vivo
study
depressive
mice
using
intraperitoneal
injection
VPALR-SUL
demonstrated
significant
increase
struggle
time
total
distance
compared
those
treated
only
while
also
reducing
concentration.
The
pharmacokinetic
results
showed
that
prolonged
half-life
increased
bioavailability.
conclusion,
exhibited
potential
for
enhancing
transport
across
BBB,
augmenting
effects,
levels.
laid
foundation
improving
delivery
developing
novel
antidepressants.
Biomedicines,
Journal Year:
2022,
Volume and Issue:
10(7), P. 1518 - 1518
Published: June 27, 2022
Gangliosides,
amphiphilic
glycosphingolipids,
tend
to
associate
laterally
with
other
membrane
constituents
and
undergo
extensive
interactions
proteins
in
cis
or
trans
configurations.
Studies
of
human
diseases
resulting
from
mutations
the
ganglioside
biosynthesis
pathway
research
on
transgenic
mice
same
implicate
gangliosides
pathogenesis
epilepsy.
Gangliosides
are
reported
affect
activity
Na+/K+-ATPase,
ubiquitously
expressed
plasma
pump
responsible
for
stabilization
resting
potential
by
hyperpolarization,
firing
up
action
ion
homeostasis.
Impaired
Na+/K+-ATPase
has
also
been
hypothesized
cause
seizures
several
mechanisms.
In
this
review
we
present
different
epileptic
phenotypes
that
caused
impaired
changed
composition.
We
further
discuss
how
may
influence
acting
as
lipid
sorting
machinery
providing
optimal
stage
function.
By
establishing
a
distinct
environment,
together
lipids,
possibly
modulate
aid
“starting
up”
“turning
off”
vital
pump.
Therefore,
structural
changes
neuronal
membranes
altered
composition
can
be
contributing
factor
leading
aberrant
imbalance
priming
neurons
pathological
firing.
Toxins,
Journal Year:
2023,
Volume and Issue:
15(9), P. 542 - 542
Published: Sept. 2, 2023
Previous
experimental
investigations
have
established
the
indispensability
of
C-terminal
Lys-Arg
residues
in
toxic
activity
AapA1
toxin
protein.
is
classified
as
a
type
I
toxin–antitoxin
(TA)
bacterial
toxin,
and
precise
impact
on
its
structure
mechanism
action
remains
elusive.
To
address
this
knowledge
gap,
present
study
employed
molecular
dynamics
(MD)
enhanced
sampling
Well-tempered
Two-dimensional
Metadynamics
(2D-MetaD)
simulations
to
examine
behavior
truncated
(AapA1-28)
within
inner
membrane
Escherichia
coli.
Specifically,
focused
elucidation
possible
conformation
states
AapA1-28
protein
POPE/POPG
(3:1)
bilayers
their
interactions
between
bilayers.
The
findings
our
investigation
indicate
that
does
not
adopt
vertical
orientation
upon
insertion;
rather,
it
assumes
an
angled
conformation,
with
side
chain
Lys-23
directed
toward
upper
layer
membrane.
This
non-transmembrane
impedes
ability
form
pores
membrane,
resulting
reduced
toxicity
towards
These
results
suggest
C-Terminal
positively
charged
are
essential
for
electrostatic
binding
negatively
head
group
bottom
bilayer
which
stabilize
transmembrane
conformation.
outcomes
contribute
comprehension
functionality
membrane-associated
proteins,
provide
improved
understanding
how
sequence
influences
antimicrobial
effect.