Eliminating Imaginary Vibrational Frequencies in Quantum-Chemical Cluster Models of Enzymatic Active Sites
Journal of Chemical Information and Modeling,
Journal Year:
2024,
Volume and Issue:
64(9), P. 3912 - 3922
Published: April 22, 2024
In
constructing
finite
models
of
enzyme
active
sites
for
quantum-chemical
calculations,
atoms
at
the
periphery
model
must
be
constrained
to
prevent
unphysical
rearrangements
during
geometry
relaxation.
A
simple
fixed-atom
or
"coordinate-lock"
approach
is
commonly
employed
but
leads
undesirable
artifacts
in
form
small
imaginary
frequencies.
These
preclude
evaluation
finite-temperature
free-energy
corrections,
limiting
thermochemical
calculations
enthalpies
only.
Full-dimensional
vibrational
frequency
are
possible
by
replacing
constraints
with
harmonic
confining
potentials.
Here,
we
compare
that
an
alternative
strategy
which
contributions
Hessian
simply
omitted.
While
latter
does
eliminate
frequencies,
it
tends
underestimate
both
zero-point
energy
and
entropy
while
introducing
artificial
rigidity.
Harmonic
potentials
frequencies
provide
a
flexible
means
construct
active-site
can
used
unconstrained
relaxations,
affording
better
convergence
reaction
energies
barrier
heights
respect
size,
as
compared
constraints.
Language: Английский
Molecular dynamics simulations for the structure-based drug design: targeting small-GTPases proteins
Expert Opinion on Drug Discovery,
Journal Year:
2024,
Volume and Issue:
19(10), P. 1259 - 1279
Published: Aug. 6, 2024
Molecular
Dynamics
(MD)
simulations
can
support
mechanism-based
drug
design.
Indeed,
MD
by
capturing
biomolecule
motions
at
finite
temperatures
reveal
hidden
binding
sites,
accurately
predict
drug-binding
poses,
and
estimate
the
thermodynamics
kinetics,
crucial
information
for
discovery
campaigns.
Small-Guanosine
Triphosphate
Phosphohydrolases
(GTPases)
regulate
a
cascade
of
signaling
events,
that
affect
most
cellular
processes.
Their
deregulation
is
linked
to
several
diseases,
making
them
appealing
targets.
The
broad
roles
small-GTPases
in
processes
recent
approval
covalent
KRas
inhibitor
as
an
anticancer
agent
renewed
interest
targeting
small-GTPase
with
small
molecules.
Language: Английский
Structural Biology of the SARS-CoV-2 replication–transcription complex
Crystallography Reviews,
Journal Year:
2025,
Volume and Issue:
unknown, P. 1 - 20
Published: March 18, 2025
Language: Английский
The Effect of Chalcogen–Chalcogen Bond Formation in the New Delhi Metallo-β-Lactamase 1 Enzyme to Counteract Antibiotic Resistance
Journal of Chemical Theory and Computation,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 24, 2024
New
Delhi
metallo-β-lactamase
1
(NDM-1)
is
an
enzyme
involved
in
the
drug
resistance
of
many
bacteria
against
most
widely
adopted
antibiotics,
such
as
penicillins,
cephalosporins,
and
carbapenems.
Consequently,
inhibiting
NDM-1
swiftly
has
gained
significant
interest
a
strategy
to
counteract
this
bacterial
defense
mechanism,
thereby
restoring
effectiveness
antibiotics.
Among
inhibitors
tested
enzyme,
ebselen
(
Language: Английский
Characterization of the Conformational Hotspots of the RNA-Dependent RNA Polymerase Complex Identifies a Unique Structural Malleability of nsp8
Sowmomita Gharui,
No information about this author
Durba Sengupta,
No information about this author
Atanu Das
No information about this author
et al.
The Journal of Physical Chemistry B,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 2, 2024
Several
antiviral
therapeutic
approaches
have
been
targeted
toward
the
RNA-dependent
RNA
polymerase
(RdRp)
complex
that
is
involved
in
viral
genome
replication.
In
SARS-CoV-2,
although
RdRp
a
multiprotein
complex,
focus
has
on
ligand
binding
catalytic
core
(nonstructural
protein
nsp12),
and
not
functional
dynamics.
this
study,
we
conformational
ensembles
of
their
modulation
by
presence
RNA,
performing
comprehensive
microsecond-scale
atomistic
simulations
apo-
RNA-bound
complex.
We
delineate
differential
impact
constituent
proteins,
such
as
polymorphisms,
dominant
segment-specific
fluctuations,
switch
dynamical
crosstalk
within
distinguish
signatures
nsp7,
nsp8,
nsp12
apo-state
are
reduced
appear
to
"prime"
for
activity.
Importantly,
identify
unique
structural
malleability
nsp8
with
high
heterogeneity
apo
state,
especially
at
three
sites
(Y71
nsp8A,
D52
A66
nsp8B).
Our
work
highlights
implications
polymorphism
structures
reveals
possibilities
development
allosteric
inhibitors.
Language: Английский