Journal of Chemical Information and Modeling,
Journal Year:
2022,
Volume and Issue:
63(1), P. 9 - 19
Published: Dec. 13, 2022
Proteases
are
major
drug
targets
for
many
viral
diseases.
However,
mutations
can
render
several
antiprotease
drugs
inefficient
rapidly
even
though
these
may
not
alter
protein
structures
significantly.
Understanding
relations
between
quickly
mutating
residues,
protease
structures,
and
the
dynamics
of
proteases
is
crucial
designing
potent
drugs.
Due
to
this
reason,
we
studied
evolutionary
information
on
residues
in
amino
acid
sequences
SARS-CoV-2
main
protease.
More
precisely,
analyzed
three
dynamical
quantities
(Schlitter
entropy,
root-mean-square
fluctuations,
flexibility
index)
their
relation
conservation
extracted
from
multiple
sequence
alignments
We
showed
that
a
quantifiable
similarity
be
built
sequence-based
quantity
called
Jensen–Shannon
those
quantities.
validated
diverse
set
32
different
proteins,
other
than
believe
establishing
kinds
quantitative
bridges
will
have
larger
implications
all
as
well
proteins.
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(3), P. 1367 - 1367
Published: Feb. 6, 2025
Severe
acute
respiratory
symptom
coronavirus
2
(SARS-CoV-2)
infection
occurs
via
the
attachment
of
spike
(S)
protein’s
receptor
binding
domain
(RBD)
to
human
ACE2
(hACE2).
Natural
polymorphisms
in
hACE2,
particularly
at
interface,
may
alter
RBD–hACE2
interactions,
potentially
affecting
viral
infectivity
across
populations.
This
study
identified
effects
six
naturally
occurring
hACE2
with
high
allele
frequency
African
population
(S19P,
K26R,
M82I,
K341R,
N546D
and
D597Q)
on
interaction
S
protein
RBD
BA.4/5
Omicron
sub-lineage
through
post-molecular
dynamics
(MD),
inter-protein
dynamic
residue
network
(DRN)
analyses.
Inter-protein
analysis
suggested
that
K26R
variation,
highest
aligns
reports
enhanced
increased
SARS-CoV-2
susceptibility.
Conversely,
S19P,
showing
fewest
interactions
largest
distances,
agrees
studies
indicating
it
hinders
binding.
The
M82I
substitution
destabilized
reducing
contact
from
92
(WT)
27.
K341R
variant,
located
distally,
had
allosteric
contacts
compared
WThACE2.
polymorphism
has
been
linked
affinity
for
Alpha,
Beta
Delta
lineages.
DRN
analyses
revealed
networks,
especially
key
residues
involved
enzyme
activity
Notably,
S19P
weaken
hACE2–RBD
while
showed
reduced
centrality
zinc
chloride-coordinating
residues,
hinting
impaired
communication
pathways.
Overall,
our
findings
show
affect
stability
modulate
influencing
infectivity—key
insights
vaccine
therapeutic
development.
Protein Science,
Journal Year:
2025,
Volume and Issue:
34(4)
Published: March 24, 2025
The
mutation
of
remote
positions
on
enzyme
scaffolds
and
how
these
residue
changes
can
affect
catalysis
is
still
far
from
being
fully
understood.
One
paradigmatic
example
the
group
lysosomal
storage
disorders,
where
activity
a
abolished
or
severely
reduced.
In
this
work,
we
analyze
molecular
dynamics
simulation
conformational
ensembles
to
unveil
features
controlling
deleterious
effects
43
reported
missense
mutations
in
human
α-mannosidase.
Using
descriptors
for
protein
dynamics,
their
coupling
with
active
site,
impact
stability,
have
assigned
contribution
each
into
connectivity
site.
We
demonstrate
here
that
use
powerful
approach
not
only
better
understand
at
level
but
also
revisit
disorders
order
aid
treatment
diseases.
