bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 11, 2024
We
develop
a
surrogate
model
for
low
complexity
disordered
proteins,
which
allows
us
to
generate
sequences
with
quantifiable
disorder.
investigate
properties
of
these
sequences,
and
show
that
the
sequence
dependence
radius
gyration
only
arises
in
vicinity
polymer
collapse
transition.
Microphase
propensity
is
shown
be
reliable
predictor,
outperforming
state
art
methods,
crossover
region.
predictions
associative
theory
as
limiting
case,
discuss
its
applicability.
Bulletin of the Korean Chemical Society,
Год журнала:
2024,
Номер
45(5), С. 420 - 434
Опубликована: Апрель 2, 2024
Abstract
Biomolecular
phase
separation
is
a
vital
mechanism
for
orchestrating
biomolecules
within
living
cells.
This
crucial
role
has
spurred
an
intense
pursuit
to
comprehend
the
molecular
underpinnings
governing
and
regulating
these
processes.
Computational
methodologies
offer
unique
perspective,
augmenting
experimental
techniques
by
providing
detailed
information
that
cannot
be
obtained
otherwise.
In
this
review,
we
briefly
overview
theoretical
computational
approaches
investigate
biomolecular
separation.
As
short
primer,
explain
factors
driving
affecting
of
biomolecules,
then
delve
into
analytical
simulation
methods
used
study
We
how
like
Flory–Huggins
theory,
random
approximation,
graph‐based
have
been
behaviors
various
proteins.
also
discuss
principles
applications
all‐atom
simulations,
coarse‐grained
field‐theoretical
approaches.
Additionally,
explore
recent
advances
in
machine
learning
approach
predict
biomolecules.
Biochemical Society Transactions,
Год журнала:
2024,
Номер
52(1), С. 319 - 329
Опубликована: Фев. 13, 2024
Intrinsically
disordered
proteins
(IDPs)
are
one
of
the
major
drivers
behind
formation
and
characteristics
biomolecular
condensates.
Due
to
their
inherent
flexibility,
backbones
IDPs
significantly
exposed,
rendering
them
highly
influential
susceptible
phase
separation.
In
densely
packed
condensates,
exposed
have
a
heightened
capacity
interact
with
neighboring
protein
chains,
which
might
lead
strong
coupling
between
secondary
structures
separation
further
modulate
subsequent
transitions
such
as
aging
fibrillization.
this
mini-review,
we
provide
an
overview
backbone-mediated
interactions
within
condensates
underscore
importance
in
We
focus
on
recent
advances
experimental
techniques
molecular
dynamics
simulation
methods
for
probing
exploring
roles
backbone
involving
IDPs.
Protein
RNA-binding
domains
selectively
interact
with
specific
RNA
sites,
a
key
interaction
that
determines
the
emergent
cooperative
behaviors
in
RNA-protein
mixtures.
Through
molecular
dynamics
simulations,
we
investigate
impact
of
binding
interactions
on
phase
transitions
an
exemplary
system
and
compare
it
predictions
Semenov–Rubinstein
theory
associative
polymers.
Our
findings
reveal
sol–gel
(percolation)
transition
without
separation,
characterized
by
double-reentrant
behavior
as
or
protein
concentration
increases.
We
highlight
crucial
role
bridge
formations
driving
these
transitions,
particularly
when
sites
are
saturated.
The
quantitatively
predicts
numbers
at
equilibrium
semidilute
regime,
but
significantly
overestimates
size
range
where
percolation
is
observed.
This
can
partly
be
traced
back
to
fact
mean-field
assumption
not
valid
dilute
regime
neglects
existence
cycles
connectivity
graph
percolating
cluster
transition.
study
enriches
understanding
behaviors,
providing
valuable
insights
for
interpretation
experimental
observations.
Agrociencia Uruguay,
Год журнала:
2025,
Номер
29(NE1), С. e1602 - e1602
Опубликована: Апрель 24, 2025
Whey,
a
byproduct
of
cheese
production,
contains
valuable
proteins
such
as
whey
protein
(WP),
which
are
key
in
the
food
industry
due
to
their
functional
properties,
especially
ability
form
gels.
When
combined
with
polysaccharides
like
carboxymethylcellulose
(CMC),
WP
can
undergo
phase
separation,
affecting
properties
viscosity
and
texture
products.
This
separation
be
segregative,
when
macromolecules
incompatible,
or
associative,
oppositely
charged
attract
each
other
networks.
study
focuses
on
CMC
mixtures
under
isoionic
conditions,
evaluating
effect
molecular
weight
rheological
mixtures.
The
tests
included
measurements
electrokinetic
potential,
microscopic
analysis,
rheology
individual
solutions
low-
high-viscosity
CMC.
It
was
found
that
tend
segregated
phases
more
easily.
flow
gelation
also
depended
concentration
type
CMC,
higher
concentrations
resulting
stronger
results
provide
insights
for
controlling
structure
functionality
systems.
Intrinsically
disordered
proteins
(IDPs)
and
biomolecular
condensates
are
critical
for
cellular
processes
physiological
functions.
Abnormal
can
cause
diseases
such
as
cancer
neurodegenerative
disorders.
IDPs,
including
intrinsically
regions
(IDRs),
were
previously
considered
undruggable
due
to
their
lack
of
stable
binding
pockets.
However,
recent
evidence
indicates
that
targeting
them
influence
processes.
This
review
explores
current
strategies
target
IDPs
condensates,
potential
improvements,
the
challenges
opportunities
in
this
evolving
field.
Intrinsically
disordered
regions
(IDRs)
play
a
critical
role
in
phase
separation
and
are
essential
for
the
formation
of
membraneless
organelles
(MLOs).
Mutations
within
IDRs
can
disrupt
their
multivalent
interaction
networks,
altering
behavior
contributing
to
various
diseases.
Therefore,
examining
evolutionary
fitness
provides
valuable
insights
into
relationship
between
protein
sequences
separation.
In
this
study,
we
utilized
ESM2
language
model
map
landscape
IDRs.
Our
findings
reveal
that
IDRs,
particularly
those
actively
participating
separation,
contain
conserved
amino
acids.
This
conservation
is
evident
through
mutational
constraints
predicted
by
supported
direct
analyses
multiple
sequence
alignments.
These
conserved,
acids
include
residues
traditionally
identified
as
“stickers”
well
“spacers”
frequently
form
continuous
motifs.
The
strong
conservation,
combined
with
suggests
these
motifs
act
functional
units
under
selection
support
stable
MLO
formation.
underscore
separation’s
molecular
grammar
made
possible
analysis
enabled
models.
Intrinsically
disordered
regions
(IDRs)
play
a
critical
role
in
phase
separation
and
are
essential
for
the
formation
of
membraneless
organelles
(MLOs).
Mutations
within
IDRs
can
disrupt
their
multivalent
interaction
networks,
altering
behavior
contributing
to
various
diseases.
Therefore,
examining
evolutionary
fitness
provides
valuable
insights
into
relationship
between
protein
sequences
separation.
In
this
study,
we
utilized
ESM2
language
model
map
landscape
IDRs.
Our
findings
reveal
that
IDRs,
particularly
those
actively
participating
separation,
contain
conserved
amino
acids.
This
conservation
is
evident
through
mutational
constraints
predicted
by
supported
direct
analyses
multiple
sequence
alignments.
These
conserved,
acids
include
residues
traditionally
identified
as
“stickers”
well
“spacers”
frequently
form
continuous
motifs.
The
strong
conservation,
combined
with
suggests
these
motifs
act
functional
units
under
selection
support
stable
MLO
formation.
underscore
separation’s
molecular
grammar
made
possible
analysis
enabled
models.
Abstract
Biomolecular
condensates
are
found
at
various
cellular
locations,
nucleus,
cytoplasm,
and
membrane.
These
often
contain
multiple
components
can
separate
into
phases
with
morphologies
such
as
core-shell
droplets,
implicating
functional
roles.
Demixing
of
their
arrangements
determined
by
competitive
interactions
locations.
Recent
studies
reported
a
puzzling
multiphase
morphology
four
postsynaptic
density:
AMPA-receptor,
NMDA-receptor,
PSD-95,
CaMKII.
The
becomes
apparently
reversed
we
move
from
the
solubilized
constructs
to
In
this
study,
using
system
model,
study
behavior
in
solution
(3D)
domain
formation
on
beneath
membrane
(2D)
elucidate
molecular
mechanisms
behind
puzzle.
Our
mesoscopic
simulations
reproduce
that
CaMKII
activation
induces
separation
3D
vitro
experiment
AMPA-receptor/PSD-95
core
NMDA-receptor/CaMKII
shell.
Then,
obtain
high
valency
large
volume
appears
be
major
factor
reversal.
Interestingly,
find
that,
while
has
dominant
non-specific
interaction
system,
specific
multivalent
overcome
for
membrane,
reversing
morphology.
On
layered
structures
receptors
CaMKIIs
reduce
effects
receptors,
making
dominant.
is
distinct
condensate
modulated
arrangement.
Abstract
Biomolecular
condensates
are
found
at
various
cellular
locations,
nucleus,
cytoplasm,
and
membrane.
These
often
contain
multiple
components
can
separate
into
phases
with
morphologies
such
as
core-shell
droplets,
implicating
functional
roles.
Demixing
of
their
arrangements
determined
by
competitive
interactions
locations.
Recent
studies
reported
a
puzzling
multiphase
morphology
four
postsynaptic
density:
AMPA-receptor,
NMDA-receptor,
PSD-95,
CaMKII.
The
becomes
apparently
reversed
we
move
from
the
solubilized
constructs
to
In
this
study,
using
system
model,
study
behavior
in
solution
(3D)
domain
formation
on
beneath
membrane
(2D)
elucidate
molecular
mechanisms
behind
puzzle.
Our
mesoscopic
simulations
reproduce
that
CaMKII
activation
induces
separation
3D
vitro
experiment
AMPA-receptor/PSD-95
core
NMDA-receptor/CaMKII
shell.
Then,
obtain
high
valency
large
volume
appears
be
major
factor
reversal.
Interestingly,
find
that,
while
has
dominant
non-specific
interaction
system,
specific
multivalent
overcome
for
membrane,
reversing
morphology.
On
layered
structures
receptors
CaMKIIs
reduce
effects
receptors,
making
dominant.
is
distinct
condensate
modulated
arrangement.
