htFuncLib: Designing libraries of active-site multipoint mutants for protein optimization
Journal of Molecular Biology,
Год журнала:
2025,
Номер
unknown, С. 169011 - 169011
Опубликована: Фев. 1, 2025
Язык: Английский
A novel directed evolution approach for co-evolution of β-glucosidase activity and organic acid tolerance
Journal of Biotechnology,
Год журнала:
2025,
Номер
401, С. 1 - 10
Опубликована: Фев. 19, 2025
Язык: Английский
Inference and visualization of complex genotype-phenotype with gpmap-tools
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Март 13, 2025
Multiplex
assays
of
variant
effect
(MAVEs)
allow
the
functional
characterization
an
unprecedented
number
sequence
variants
in
both
gene
regulatory
regions
and
protein
coding
sequences.
This
has
enabled
study
nearly
complete
combinatorial
libraries
mutational
revealed
widespread
influence
higher-order
genetic
interactions
that
arise
when
multiple
mutations
are
combined.
However,
lack
appropriate
tools
for
exploratory
analysis
this
high-dimensional
data
limits
our
overall
understanding
main
qualitative
properties
complex
genotype-phenotype
maps.
To
fill
gap,
we
have
developed
gpmap-tools
(
https://github.com/cmarti/gpmap-tools
),
a
python
library
integrates
Gaussian
process
models
inference,
phenotypic
imputation,
error
estimation
from
incomplete
noisy
MAVE
collections
natural
sequences,
together
with
methods
summarizing
patterns
epistasis
non-linear
dimensionality
reduction
techniques
visualization
maps
containing
up
to
millions
genotypes.
Here,
used
map
Shine-Dalgarno
sequence,
motif
modulates
binding
16S
rRNA
5'
untranslated
region
(UTR)
mRNAs
through
base
pair
complementarity
during
translation
initiation
prokaryotes.
We
inferred
full
landscapes
262,144
different
sequences
5,311
5'UTRs
E.
coli
genome
experimental
data.
Visualizations
were
largely
consistent
each
other,
unveiled
simple
molecular
mechanism
underlying
highly
epistatic
sequence.
Язык: Английский
Evolutionary paths that link orthogonal pairs of binding proteins
Cell Systems,
Год журнала:
2025,
Номер
unknown, С. 101262 - 101262
Опубликована: Апрель 1, 2025
Язык: Английский
Encoding and decoding selectivity and promiscuity in the human chemokine-GPCR interaction network
Cell,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 1, 2025
Язык: Английский
Protein folding: From physico-chemical rules and cellular machineries of protein quality control to AI solutions
Proceedings of the National Academy of Sciences,
Год журнала:
2024,
Номер
121(34)
Опубликована: Авг. 12, 2024
Large
volumes
of
liquid
water
transiently
existed
on
the
surface
Mars
more
than
3
billion
years
ago.
Much
this
is
hypothesized
to
have
been
sequestered
in
subsurface
or
lost
space.
We
use
rock
physics
models
and
Bayesian
inversion
...
Язык: Английский
GGAssembler: Precise and economical design and synthesis of combinatorial mutation libraries
Protein Science,
Год журнала:
2024,
Номер
33(10)
Опубликована: Сен. 16, 2024
Abstract
Golden
Gate
assembly
(GGA)
can
seamlessly
generate
full‐length
genes
from
DNA
fragments.
In
principle,
GGA
could
be
used
to
design
combinatorial
mutation
libraries
for
protein
engineering,
but
creating
accurate,
complex,
and
cost‐effective
has
been
challenging.
We
present
GGAssembler,
a
graph‐theoretical
method
economical
of
fragments
that
assemble
library
encodes
any
desired
diversity.
GGAssembler
one‐pot
in
vitro
camelid
antibody
comprising
>10
5
variants
with
costs
<0.007$
per
variant
dropping
significantly
increased
complexity.
>93%
the
were
product
>99%
represented
within
expected
order
magnitude
as
verified
by
deep
sequencing.
The
workflow
is,
therefore,
an
accurate
approach
generating
complex
may
drastically
reduce
accelerate
discovery
optimization
antibodies,
enzymes
other
proteins.
is
accessible
through
Google
Colab
notebook
at
https://github.com/Fleishman-Lab/GGAssembler
.
Язык: Английский