Structural and Dynamical Basis of VP35-RBD Inhibition by Marine Fungi Compounds to Combat Marburg Virus Infection
Marine Drugs,
Год журнала:
2024,
Номер
22(1), С. 34 - 34
Опубликована: Янв. 3, 2024
The
Marburg
virus
(MBV),
a
deadly
pathogen,
poses
serious
threat
to
world
health
due
the
lack
of
effective
treatments,
calling
for
an
immediate
search
targeted
and
efficient
treatments.
In
this
study,
we
focused
on
compounds
originating
from
marine
fungi
in
order
identify
possible
inhibitory
against
(MBV)
VP35-RNA
binding
domain
(VP35-RBD)
using
computational
approach.
We
started
with
virtual
screening
procedure
Lipinski
filter
as
guide.
Based
their
docking
scores,
42
potential
candidates
were
found.
Four
these
compounds—CMNPD17596,
CMNPD22144,
CMNPD25994,
CMNPD17598—as
well
myricetin,
control
compound,
chosen
re-docking
analysis.
Re-docking
revealed
that
particular
had
higher
affinity
MBV
VP35-RBD
comparison
control.
Analyzing
chemical
interactions
unique
properties
every
identified
by
range
Pi–cation
hydrogen
bond
types.
able
learn
more
about
dynamic
behaviors
stability
protein–ligand
complexes
through
200-nanosecond
molecular
dynamics
simulation,
demonstrated
compounds’
consistent
RMSD
RMSF
values.
multidimensional
nature
data
was
clarified
application
principal
component
analysis,
which
suggested
stable
conformations
little
modification.
Further
insight
into
energy
profiles
states
also
obtained
examination
free
landscape.
Our
findings
underscore
effectiveness
strategies
identifying
analyzing
inhibitors
VP35-RBD,
offering
promising
paths
further
experimental
investigations
therapeutic
development
MBV.
Язык: Английский
Antifungal drug discovery for targeting Candida albicans morphogenesis through structural dynamics study
Journal of Biomolecular Structure and Dynamics,
Год журнала:
2024,
Номер
unknown, С. 1 - 17
Опубликована: Апрель 18, 2024
In
response
to
the
escalating
threat
of
drug-resistant
fungi
human
health,
there
is
an
urgent
need
for
innovative
strategies.
Our
focus
on
addressing
this
challenge
by
exploring
a
previously
untapped
target,
yeast
casein
kinase
(Yck2),
as
potential
space
antifungal
development.
To
identify
promising
candidates,
we
conducted
thorough
screening
diverse-lib
drug-like
molecule
library,
comprising
99,288
molecules.
Five
notable
compounds
with
IDs
24334243,
24342416,
17516746,
17407455,
and
24360740
were
selected
based
their
binding
energy
scores
surpassing
11
Kcal/mol.
investigation
delved
into
interaction
studies
dynamic
stability
these
compounds.
Remarkably,
all
molecules
demonstrated
acceptable
RMSD
values
during
200
ns
simulation,
indicating
stable
nature.
Further
analysis
through
Principal
Component
Analysis
(PCA)-based
Free
Energy
Landscape
(FEL)
revealed
minimal
transitions
most
compounds,
signifying
stability.
Notably,
two
exhibited
slightly
different
behaviour
in
terms
transitions.
These
findings
mark
significant
breakthrough
realm
drugs
against
C.
albicans
targeting
Yck2
protein.
However,
it
crucial
note
that
additional
experimental
validation
imperative
assess
efficacy
candidates.
This
study
serves
starting
point
further
exploration
development
quest
effective
solutions.
Язык: Английский
Computational exploration of Zika virus RNA-dependent RNA polymerase inhibitors: a promising antiviral drug discovery approach
Journal of Biomolecular Structure and Dynamics,
Год журнала:
2023,
Номер
unknown, С. 1 - 12
Опубликована: Дек. 12, 2023
The
emergence
of
the
Zika
virus,
which
belongs
to
Flaviviridae
family,
became
a
significant
worldwide
health
issue
due
its
link
with
severe
neurological
complications.
RNA-dependent
RNA
polymerase
(RdRp)
virus
plays
part
in
replication
and
is
considered
promising
candidate
for
antiviral
drug
identification.
In
this
study,
we
employed
computer-based
discovery
approaches
identify
potential
natural
compounds
that
could
act
as
inhibitors
against
RdRp
protein
virus.
A
comprehensive
virtual
screening
strategy
was
implemented
using
MTiOpenScreen
webserver
from
NP-Lib
database.
Four
having
ZINC
ID
–
ZINC000253499147,
ZINC000299817665,
ZINC000044404209,
ZINC000253388535
were
selected
based
on
binding
score
revealed
during
screening.
Molecular
docking
simulations
these
reference
performed
assess
affinities
molecular
bonds
formed
docking.
Additionally,
dynamics
(MD)
simulations,
endpoint
free
energy
calculation
principal
component
analysis
(PCA)
evaluate
stability
protein-ligand
complexes.
These
exhibited
favourable
energies
stable
interactions
within
active
site
protein.
Moreover,
robustness
complexes,
suggesting
sustained
inhibition.
findings
provide
valuable
insights
design
development
novel
therapeutic
interventions
infection.
Further
experimental
validation
optimization
identified
are
warranted
advance
their
translation
into
effective
drugs.
Язык: Английский
Investigating the bispecific lead compounds against methicillin-resistant Staphylococcus aureus SarA and CrtM using machine learning and molecular dynamics approach
Journal of Biomolecular Structure and Dynamics,
Год журнала:
2023,
Номер
unknown, С. 1 - 18
Опубликована: Дек. 26, 2023
Methicillin-resistant
Staphylococcus
aureus
(MRSA)
is
a
notorious
pathogen
that
has
emerged
as
serious
global
health
concern
over
the
past
few
decades.
Staphylococcal
accessory
regulator
A
(SarA)
and
4,4′-diapophytoene
synthase
(CrtM)
play
crucial
role
in
biofilm
formation
staphyloxanthin
biosynthesis.
Thus,
present
study
used
machine
learning-based
QSAR
model
to
screen
1261
plant-derived
natural
organic
compounds
order
identify
medication
candidate
with
both
virulence
inhibitory
potential.
Additionally,
in-silico
molecular
docking
analysis
demonstrated
significant
binding
efficacy
of
identified
hit
compound,
85137543,
SarA
CrtM
when
compared
control
hesperidin.
Post-MD
simulation
complexes
depicted
strong
85137543
CrtM.
Moreover,
showed
hydrogen
bonding
key
residues
proteins
during
(ALA138
ALA134
CrtM)
post-MD
(LYS273
ASN212
SarA).
The
RMSD
was
stable
consistent
bound
RMSDs
1.3
1
nm,
respectively.
In
addition,
principal
component
free
energy
landscape
complex
proteins.
Low
(ΔGTotal)
observed
by
for
(−47.92
kcal/mol)
(−36.43
kcal/mol),
which
binding.
Overall,
this
potential
inhibitor
MRSA.
Язык: Английский
Investigating the effects of four medicinal plants against dengue virus through QSAR modeling and molecular dynamics studies
Journal of Biomolecular Structure and Dynamics,
Год журнала:
2024,
Номер
unknown, С. 1 - 18
Опубликована: Янв. 10, 2024
The
Dengue
virus
(DENV)
has
been
increasingly
recognized
as
a
prevalent
viral
pathogen
responsible
for
global
transmission
of
infection.
It
established
that
DENV's
NS5
methyltransferase
(MTase)
controls
replication.
As
result,
MTase
is
considered
potentially
useful
drug
target
DENV.
In
this
study,
the
two
phases
virtual
screening
were
conducted
using
ML-based
QSAR
model
and
molecular
docking
to
identify
potential
compounds
against
Four
medicinal
plants
[Aloe
vera,
Cannabis
sativa
(Hemp),
Ocimum
sanctum
(Holy
Basil;
Tulsi),
Zingiber
officinale
(Ginger)]
showed
anti-viral
properties
selected
sourcing
phytochemicals
them
NS5.
Additionally,
re-docking
at
higher
exhaustiveness
interaction
analysis
performed
which
resulted
in
identification
top
four
hits
(135398658,
5281675,
119394,
969516)
comparable
results
with
control
Sinefungin
(SFG).
Post
dynamics
simulation,
135398658
lowest
RMSD
(0.4–0.5
nm)
maximum
number
hydrogen
bonds
(eight
bonds)
after
while
5281675
969516
control.
These
direct
interactions
catalytic
site
residues
GLU111
ASP131,
addition
these
stable
complex
formation
depicted
by
principal
component
free
energy
landscape.
lower
total
binding
(ΔGTotal
=
−36.56
kcal/mol)
than
control,
had
values
−34.1
kcal/mol).
Overall,
purpose
study
was
inhibit
function,
could
be
further
tested
experimentally
treat
dengue
(DENV).
Язык: Английский
Application of temperature-dependent and steered molecular dynamics simulation to screen anti-dengue compounds against Marburg virus
Journal of Biomolecular Structure and Dynamics,
Год журнала:
2024,
Номер
unknown, С. 1 - 20
Опубликована: Янв. 17, 2024
Marburg
virus
infections
are
extremely
fatal
with
a
fatality
range
of
23%
to
90%,
therefore
there
is
an
urgent
requirement
design
and
develop
efficient
therapeutic
molecules.
Here,
comprehensive
temperature-dependent
molecular
dynamics
(MD)
simulation
method
was
implemented
identify
the
potential
molecule
from
anti-dengue
compound
library
that
can
inhibit
function
VP24
protein
Marburg.
Virtual
high
throughput
screening
identified
five
effective
binders
after
484
compounds.
These
compounds
were
treated
in
MD
at
four
different
temperatures:
300,
340,
380,
420
K.
Higher
temperatures
showed
dissociation
hit
protein.
Further,
triplicates
100
ns
conducted
which
ID
=
118717693,
5361
strong
stability
molecule.
further
validated
using
ΔG
binding
free
energies
they
showed:
−30.38
kcal/mol,
−67.83
kcal/mol
energies,
respectively.
Later,
these
two
used
steered
detect
its
dissociation.
Compound
maximum
pulling
force
199.02
kcal/mol/nm
dissociate
protein-ligand
complex
while
118717693
had
101.11
kcal/mol/nm,
This
ligand
highest
number
hydrogen
bonds
varying
occupancies
89.93%,
69.80%,
57.93%,
52.33%,
50.63%.
study
bind
strongly
has
be
in-vitro
experiment.
Язык: Английский
Computational insights into overcoming resistance mechanisms in targeted therapies for advanced breast cancer: focus on EGFR and HER2 co-inhibition
Journal of Biomolecular Structure and Dynamics,
Год журнала:
2024,
Номер
unknown, С. 1 - 12
Опубликована: Янв. 17, 2024
In
the
present
study,
formation
of
a
heterodimer
involving
both
epidermal
growth
factor
receptor
(EGFR)
and
human
2
(HER2)
has
been
explored
as
potential
therapeutic
mechanism
to
inhibit
progression
breast
cancer.
Virtual
screening
using
molecular
docking
resulted
in
three
hit
compounds
(ZINC08382411,
ZINC08382438,
ZINC08382292)
with
minimum
binding
scores
commonly
receptors.
Further,
MD
simulation
analysis
these
complexes
illustrated
high
stability
EGFR
HER2.
RMSD
showed
that
ZINC08382411
displayed
most
stable
-
3
Å
when
bound
receptors,
suggesting
have
strong
compatibility
active
site
receptor.
Hydrogen
bond
forms
maximum
number
H-bonds
(2
3)
HER2
complexes,
highest
occupancy
62%
79%,
respectively.
Binding
free
energy
calculation
possesses
affinity
towards
receptors
ΔGbind
=
−129.628
−164.063
kJ/mol,
This
approach
recognizes
significance
cancer
development
aims
disrupt
their
collaborative
signaling,
which
is
known
promote
antagonistic
behavior
cells.
By
focusing
on
this
EGFR/HER2
heterodimer,
study
offers
promising
avenue
for
identifying
candidate
(ZINC08382411)
may
cell
potentially
improve
patient
outcomes.
The
study's
findings
contribute
ongoing
efforts
advance
treatment
strategies.
Язык: Английский
A simulation-based approach to target Zika virus RNA-dependent RNA polymerase with marine compounds for antiviral development
Journal of Biomolecular Structure and Dynamics,
Год журнала:
2024,
Номер
unknown, С. 1 - 11
Опубликована: Фев. 28, 2024
Despite
significant
efforts,
currently,
there
is
no
particular
drug
available
to
treat
Zika
virus
(ZIKV)
infection,
highlighting
the
urgent
need
for
effective
therapeutic
interventions.
To
identify
putative
inhibitors
of
ZIKV
RdRp
protein's
RNA
binding
function,
present
study
applied
an
extensive
in-silico
discovery
methodology.
The
initial
phase
involved
virtual
screening
using
Lipinski's
rule
five
as
a
filter,
ensuring
selection
molecules
with
favorable
pharmacokinetic
properties.
This
process
yielded
238
compounds
promising
docking
scores,
ranging
from
−6.0
−7.48
kcal/mol,
indicative
their
potential
affinity
RdRp.
refine
selection,
these
underwent
re-docking
process,
comparing
energies
reference
molecule
known
its
inhibitory
action
against
Remarkably,
compounds,
labeled
CMNPD30598,
CMNPD27464,
CMNPD25971,
CMNPD27444,
and
CMNPD16599,
demonstrated
superior
compared
reference,
suggesting
stronger
interaction
allosteric
site.
Subsequent
molecular
dynamics
(MD)
simulations
provided
insights
into
stability
complexes
over
time,
reinforcing
inhibitors.
Additionally,
calculation
free
principal
component
analysis
(PCA)
energy
landscape
offered
deeper
understanding
energetics.
not
only
highlights
utility
marine
fungi
in
antiviral
but
also
showcases
power
computational
tools
identifying
novel
therapeutics.
identified
represent
candidates
further
experimental
validation
development
Язык: Английский