The Journal of Physical Chemistry A,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 3, 2024
Automated
and
high-throughput
quantum
chemical
investigations
into
processes
have
become
feasible
in
great
detail
broad
scope.
This
results
an
increase
complexity
of
the
tasks
amount
generated
data.
An
efficient
intuitive
way
for
operator
to
interact
with
these
data
steer
virtual
experiments
is
required.
Here,
we
introduce
Heron,
a
graphical
user
interface
that
allows
advanced
human-machine
interactions
exploration
campaigns
molecular
structure
reactivity.
Heron
offers
access
interactive
automated
explorations
reactions
standard
electronic
modules,
haptic
force
feedback,
microkinetic
modeling,
refinement
by
correlated
calculations
including
black-box
complete
active
space
calculations.
It
tailored
analysis
vast
reaction
networks.
We
show
how
interoperable
modules
enable
workflows
pave
routine
low-entrance-barrier
modeling
techniques.
Journal of Chemical Theory and Computation,
Год журнала:
2023,
Номер
19(15), С. 5007 - 5023
Опубликована: Июль 3, 2023
A
reaction
route
map
(RRM)
constructed
using
the
GRRM
program
is
a
collection
of
elementary
pathways,
each
which
comprises
two
equilibrium
(EQ)
geometries
and
one
transition
state
(TS)
geometry
connected
by
an
intrinsic
coordinate
(IRC).
An
RRM
can
be
mathematically
represented
graph
with
weights
assigned
to
both
vertices,
corresponding
EQs,
edges,
TSs,
representing
energies.
In
this
study,
we
propose
method
extract
topological
descriptors
weighted
based
on
persistent
homology
(PH).
The
work
Mirth
et
al.
[
J.
Chem.
Phys.2021,
154,
114114],
in
PH
analysis
was
applied
(3N
-
6)-dimensional
potential
energy
surface
N
atomic
system,
related
present
method,
but
our
practically
applicable
realistic
molecular
reactions.
Numerical
assessments
revealed
that
same
information
as
proposed
for
0-th
1-st
PHs,
except
death
PH.
addition,
obtained
from
corresponds
disconnectivity
graph.
results
study
suggest
accurately
reflect
characteristics
chemical
reactions
and/or
physicochemical
properties
system.
ACS Central Science,
Год журнала:
2024,
Номер
10(2), С. 302 - 314
Опубликована: Янв. 31, 2024
In
recent
years,
first-principles
exploration
of
chemical
reaction
space
has
provided
valuable
insights
into
intricate
networks.
Here,
we
introduce
ab
initio
hyperreactor
dynamics,
which
enables
rapid
screening
the
accessible
from
a
given
set
initial
molecular
species,
predicting
new
synthetic
routes
that
can
potentially
guide
subsequent
experimental
studies.
For
this
purpose,
different
hyperdynamics
derived
bias
potentials
are
applied
along
with
pressure-inducing
spherical
confinement
system
in
dynamics
simulations
to
efficiently
enhance
reactivity
under
mild
conditions.
To
showcase
advantages
and
flexibility
approach,
present
systematic
study
method's
parameters
on
HCN
toy
model
apply
it
recently
introduced
for
prebiotic
formation
glycinal
acetamide
interstellar
ices,
yields
results
line
findings.
addition,
show
how
developed
framework
complicated
transitions
like
first
step
nonenzymatic
DNA
nucleoside
synthesis
an
aqueous
environment,
where
fragmentation
problem
earlier
nanoreactor
approaches
is
avoided.
Journal of Chemical Theory and Computation,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 1, 2025
The
parallel
on-the-fly
Crystal
algorithm
is
a
new,
efficient
global
search
for
exploring
single-state
potential
energy
surfaces
and
conical
intersection
seam
spaces
of
wide
range
molecules.
Despite
major
developments,
its
application
to
complex
molecular
systems,
especially
in
the
condensed
phase,
remains
challenging
due
high
dimensionality
configurational
space.
In
this
work,
we
address
challenge
extend
applicability
reaction
discovery
large
photoswitches
various
environments,
including
phase
with
explicit
solvent
This
achieved
by
performing
an
exploration
comparatively
subspace,
while
gradually
relaxing
remaining
degrees
freedom.
new
applied
bilirubin
donor-acceptor
Stenhouse
adducts,
next-generation
class
photoswitches,
vacuum
aqueous
solution.
To
end,
designed
automated
systematic
workflow
discover
characterize
minima
low-energy
pathways
these
systems.
Our
findings
demonstrate
algorithm's
effectiveness
quickly
configuration
space
uncovering
kinetically
accessible
products,
offering
insights
into
intricate
chemical
reactivities
molecules
roles
environments
on
pathways.
results
underscore
promising
parallelized
methods
biomolecular
Journal of Chemical Theory and Computation,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 28, 2025
Describing
chemical
reactions
in
solution
on
a
molecular
level
is
challenging
task
due
to
the
high
mobility
of
weakly
interacting
solvent
molecules
which
requires
configurational
sampling.
For
instance,
polar
and
protic
solvents
can
interact
strongly
with
solutes
may
interfere
reactions.
To
define
identify
representative
arrangements
modulating
transition
state
nontrivial
task.
Here,
we
propose
monitor
their
active
participation
decaying
normal
mode
at
state,
defines
molecules.
Moreover,
it
desirable
prepare
low-dimensional
microsolvation
model
well-defined,
fully
automated,
high-throughput,
easy-to-deploy
fashion,
derive
stepwise
protocol.
First,
structures
are
optimized
sufficiently
solvated
quantum-classical
hybrid
model,
subjected
redefinition
then
reduced
quantum
region.
From
minimally
microsolvated
extracted
that
contain
only
Modeling
remaining
solvation
effects
deferred
continuum
model.
establish
an
easy-to-use
free-energy
combine
standard
thermochemical
gas-phase
correction
for
cavity
entropy
solution.
We
assess
our
models
methanediol
formation
from
formaldehyde;
hydration
carbon
dioxide
(which
consider
mixture
demonstrate
versatility
approach);
and,
finally,
chlorination
phenol
hypochlorous
acid.
PLoS ONE,
Год журнала:
2024,
Номер
19(11), С. e0308969 - e0308969
Опубликована: Ноя. 25, 2024
Malaria
which
is
mainly
caused
by
Plasmodium
falciparum
parasite
remains
a
devastating
public
health
concern,
necessitating
the
need
to
develop
new
antimalarial
agents.
P.
heat
shock
protein
90
(Hsp90),
indispensable
for
survival
and
promising
drug
target.
Inhibitors
targeting
ATP-binding
pocket
of
N-terminal
domain
have
anti-Plasmodium
effects.
We
proposed
de
novo
active
learning
(AL)
driven
method
in
tandem
with
docking
predict
inhibitors
unique
scaffolds
preferential
selectivity
towards
PfHsp90.
Reference
compounds,
predicted
bind
PfHsp90
at
possessing
activities,
were
used
generate
10,000
derivatives
build
Auto-quantitative
structures
activity
relationships
(QSAR)
models.
Glide
was
performed
scores
>
15,000
compounds
obtained
from
ChEMBL
database.
Re-iterative
training
testing
models
until
optimum
Kennel-based
Partial
Least
Square
(KPLS)
regression
model
coefficient
R2
=
0.75
set
squared
correlation
prediction
Q2
0.62
test
reached
convergence.
Rescoring
using
induced
fit
molecular
dynamics
simulations
enabled
us
prioritize
15
ATP/ADP-like
design
ideas
purchase.
The
exerted
moderate
NF54
strain
IC50
values
≤
6μM
displayed
weak
affinity
(KD
range:
13.5-19.9μM)
comparable
reported
ADP.
most
potent
compound
FTN-T5
(PfN54
IC50:1.44μM;
HepG2/CHO
cells
SI≥
29)
bound
(KD:7.7μM),
providing
starting
point
optimization
efforts.
Our
work
demonstrates
great
utility
AL
rapid
identification
novel
molecules
discovery
(i.e.,
hit
identification).
potency
will
be
critical
designing
species-selective
developing
more
efficient
agents
against
malaria.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Май 18, 2024
Abstract
Malaria
which
is
mainly
caused
by
Plasmodium
falciparum
parasite
remains
a
devastating
public
health
concern,
necessitating
the
need
to
develop
new
antimalarial
agents.
P.
heat
shock
protein
90
(Hsp90),
indispensable
for
survival
and
promising
drug
target.
Inhibitors
targeting
ATP-binding
pocket
of
N-terminal
domain
have
anti-
effects.
We
proposed
de
novo
active
learning
(AL)
driven
method
in
tandem
with
docking
predict
inhibitors
unique
scaffolds
preferential
selectivity
towards
PfHsp90.
Reference
compounds,
predicted
bind
PfHsp90
at
possessing
activities,
were
used
generate
10,000
derivatives
build
Auto-quantitative
structures
activity
relationships
(QSAR)
models.
Glide
was
performed
scores
>
15,000
compounds
obtained
from
ChEMBL
database.
Re-iterative
training
testing
models
until
optimum
Kennel-based
Partial
Least
Square
(KPLS)
regression
model
coefficient
R2
=
0.75
set
squared
correlation
prediction
Q2
0.62
test
reached
convergence.
Rescoring
using
induced
fit
molecular
dynamics
simulations
enabled
us
prioritize
15
ATP/ADP-like
design
ideas
purchase.
The
exerted
moderate
NF54
strain
IC
50
values
≤
6μM
displayed
weak
affinity
(K
D
range:
13.5-19.9μM)
comparable
reported
ADP.
most
potent
compound
FTN-T5
(PfN54
:1.44μM;
HepG2/CHO
cells
SI≥
29)
bound
:7.7μM),
providing
starting
point
optimization
efforts.
Our
work
demonstrates
great
utility
AL
rapid
identification
novel
molecules
discovery
(i.e.,
hit
identification).
potency
will
be
critical
designing
species-selective
developing
more
efficient
agents
against
malaria.
Digital Discovery,
Год журнала:
2024,
Номер
3(9), С. 1682 - 1694
Опубликована: Янв. 1, 2024
We
present
graph
databases
as
a
modern
solution
for
storing
and
accessing
chemical
knowledge.
This
approach
is
demonstrated
in
commercial
route
selection
holds
the
potential
to
create
universal
data-sharing
framework
chemistry.
Journal of Chemical Theory and Computation,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 6, 2024
Exploring
potential
energy
surfaces
(PES)
is
essential
for
unraveling
the
underlying
mechanisms
of
chemical
reactions
and
material
properties.
While
activation-relaxation
technique
(ARTn)
a
state-of-the-art
method
identifying
saddle
points
on
PES,
it
often
faces
challenges
in
complex
landscapes,
especially
surfaces.
In
this
study,
we
introduce
iso-ARTn,
an
enhanced
ARTn
that
incorporates
constraints
orthogonal
hyperplane
employs
adaptive
active
volume.
By
leveraging
neural
network
(NNP)
to
conduct
exhaustive
point
search
Pt(111)
surface
with
0.3
monolayers
oxygen
coverage,
iso-ARTn
achieves
success
rate
8.2%
higher
than
original
ARTn,
40%
fewer
force
calls.
Moreover,
effectively
finds
various
without
compromising
rate.
Combined
kinetic
Monte
Carlo
simulations
event
table
construction,
NNP
demonstrates
capability
reveal
structures
consistent
experimental
observations.
This
work
signifies
substantial
advancement
investigation
enhancing
both
efficiency
breadth
searches.