Joseph L. Watson
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View article: De-novo design of a random protein walker
De-novo design of a random protein walker Open
Molecular machines hold great potential. Design of static monomeric and oligomeric protein structures has advanced tremendously, but few dynamic protein systems have been designed. Here we present the design and characterization of a rando…
View article: Parametrically guided design of beta barrels and transmembrane nanopores using deep learning
Parametrically guided design of beta barrels and transmembrane nanopores using deep learning Open
Francis Crick’s global parameterization of coiled coil geometry has been widely useful for guiding design of new protein structures and functions. However, design guided by similar global parameterization of beta barrel structures has been…
View article: Diffusing protein binders to intrinsically disordered proteins
Diffusing protein binders to intrinsically disordered proteins Open
View article: ANXA11 biomolecular condensates facilitate protein-lipid phase coupling on lysosomal membranes
ANXA11 biomolecular condensates facilitate protein-lipid phase coupling on lysosomal membranes Open
View article: MotifBench: A standardized protein design benchmark for motif-scaffolding problems
MotifBench: A standardized protein design benchmark for motif-scaffolding problems Open
The motif-scaffolding problem is a central task in computational protein design: Given the coordinates of atoms in a geometry chosen to confer a desired biochemical function (a motif), the task is to identify diverse protein structures (sc…
View article: Improved protein binder design using beta-pairing targeted RFdiffusion
Improved protein binder design using beta-pairing targeted RFdiffusion Open
Despite recent advances in the computational design of protein binders, designing proteins that bind with high affinity to polar protein targets remains an outstanding problem. Here we show that RFdiffusion can be conditioned to efficientl…
View article: Correction to: Synthetic Engineering of Cortical Polarity During Mitosis Using Designed Proteins
Correction to: Synthetic Engineering of Cortical Polarity During Mitosis Using Designed Proteins Open
View article: Bottom-up design of calcium channels from defined selectivity filter geometry
Bottom-up design of calcium channels from defined selectivity filter geometry Open
Native ion channels play key roles in biological systems, and engineered versions are widely used as chemogenetic tools and in sensing devices 1,2 . Protein design has been harnessed to generate pore-containing transmembrane proteins, but …
View article: Synthetic Engineering of Cortical Polarity During Mitosis Using Designed Proteins
Synthetic Engineering of Cortical Polarity During Mitosis Using Designed Proteins Open
During asymmetric cell division, cortical polarity cues drive the polarization of the microtubule cytoskeleton to ensure the generation of two daughter cells with different fates. While this a critical process for development and tissue ho…
View article: Improved protein binder design using beta-pairing targeted RFdiffusion
Improved protein binder design using beta-pairing targeted RFdiffusion Open
Despite recent advances in the computational design of protein binders, designing proteins that bind with high affinity to polar protein targets remains an outstanding problem. Here we show that RFdiffusion can be conditioned to efficientl…
View article: Nucleation limited assembly and polarized growth of a <i>de novo</i>-designed allosterically modulatable protein filament
Nucleation limited assembly and polarized growth of a <i>de novo</i>-designed allosterically modulatable protein filament Open
The design of inducibly assembling protein nanomaterials is an outstanding challenge. Here, we describe the computational design of a protein filament formed from a monomeric subunit that binds a peptide ligand. The cryoEM structure of the…
View article: Accurate single domain scaffolding of three non-overlapping protein epitopes using deep learning
Accurate single domain scaffolding of three non-overlapping protein epitopes using deep learning Open
De novo protein design has seen major success in scaffolding single functional motifs, however, in nature most proteins present multiple functional sites. Here we describe an approach to simultaneously scaffold multiple functional sites in…
View article: Parametrically guided design of beta barrels and transmembrane nanopores using deep learning
Parametrically guided design of beta barrels and transmembrane nanopores using deep learning Open
Francis Crick’s global parameterization of coiled coil geometry has been widely useful for guiding design of new protein structures and functions. However, design guided by similar global parameterization of beta barrel structures has been…
View article: Diffusing protein binders to intrinsically disordered proteins
Diffusing protein binders to intrinsically disordered proteins Open
Proteins which bind intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) with high affinity and specificity could have considerable utility for therapeutic and diagnostic applications. However, a general met…
View article: Accurate single domain scaffolding of three non-overlapping protein epitopes using deep learning
Accurate single domain scaffolding of three non-overlapping protein epitopes using deep learning Open
De novo protein design has seen major success in scaffolding single functional motifs, however, in nature most proteins present multiple functional sites. Here we describe an approach to simultaneously scaffold multiple functional sites in…
View article: A role for vessel‐associated extracellular matrix proteins in multiple sclerosis pathology
A role for vessel‐associated extracellular matrix proteins in multiple sclerosis pathology Open
Multiple sclerosis (MS) is unsurpassed for its clinical and pathological hetherogeneity, but the biological determinants of this variability are unknown. HLA‐DRB1*15 , the main genetic risk factor for MS, influences the severity and distri…
View article: Author Correction: Macromolecular condensation buffers intracellular water potential
Author Correction: Macromolecular condensation buffers intracellular water potential Open
View article: De novo design of pH-responsive self-assembling helical protein filaments
De novo design of pH-responsive self-assembling helical protein filaments Open
Biological evolution has led to precise and dynamic nanostructures that reconfigure in response to pH and other environmental conditions. However, designing micrometre-scale protein nanostructures that are environmentally responsive remain…
View article: Atomically accurate de novo design of antibodies with RFdiffusion
Atomically accurate de novo design of antibodies with RFdiffusion Open
Despite the central role that antibodies play in modern medicine, there is currently no method to design novel antibodies that bind a specific epitope entirely in silico . Instead, antibody discovery currently relies on animal immunization…
View article: De novo design of high-affinity binders of bioactive helical peptides
De novo design of high-affinity binders of bioactive helical peptides Open
View article: <scp>HEATR5B</scp> associates with dynein‐dynactin and promotes motility of <scp>AP1</scp> ‐bound endosomal membranes
<span>HEATR5B</span> associates with dynein‐dynactin and promotes motility of <span>AP1</span> ‐bound endosomal membranes Open
The microtubule motor dynein mediates polarised trafficking of a wide variety of organelles, vesicles and macromolecules. These functions are dependent on the dynactin complex, which helps recruit cargoes to dynein's tail and activates mot…
View article: Macromolecular condensation buffers intracellular water potential
Macromolecular condensation buffers intracellular water potential Open
View article: Synthetic Par polarity induces cytoskeleton asymmetry in unpolarized mammalian cells
Synthetic Par polarity induces cytoskeleton asymmetry in unpolarized mammalian cells Open
Polarized cells rely on a polarized cytoskeleton to function. Yet, how cortical polarity cues induce cytoskeleton polarization remains elusive. Here, we capitalized on recently established designed 2D protein arrays to ectopically engineer…
View article: Zero‐shot mutation effect prediction on protein stability and function using <scp>RoseTTAFold</scp>
Zero‐shot mutation effect prediction on protein stability and function using <span>RoseTTAFold</span> Open
Predicting the effects of mutations on protein function and stability is an outstanding challenge. Here, we assess the performance of a variant of RoseTTAFold jointly trained for sequence and structure recovery, RF joint , for mutation eff…
View article: De novo design of protein structure and function with RFdiffusion
De novo design of protein structure and function with RFdiffusion Open
There has been considerable recent progress in designing new proteins using deep-learning methods 1–9 . Despite this progress, a general deep-learning framework for protein design that enables solution of a wide range of design challenges,…
View article: ANXA11 biomolecular condensates facilitate protein-lipid phase coupling on lysosomal membranes
ANXA11 biomolecular condensates facilitate protein-lipid phase coupling on lysosomal membranes Open
SUMMARY Phase transitions of cellular proteins and lipids play a key role in governing the organisation and coordination of intracellular biology. The frequent juxtaposition of proteinaceous biomolecular condensates to cellular membranes r…
View article: HEATR5B associates with dynein-dynactin and selectively promotes motility of AP1-bound endosomal membranes
HEATR5B associates with dynein-dynactin and selectively promotes motility of AP1-bound endosomal membranes Open
The dynein motor complex mediates polarised trafficking of a wide variety of organelles, intracellular vesicles and macromolecules. These functions are dependent on the dynactin complex, which helps recruit cargoes to dynein’s tail region …
View article: Mutation Effect Prediction of Proteins using RoseTTAFold
Mutation Effect Prediction of Proteins using RoseTTAFold Open
Deep mutational scanning datasets used for 'Mutation Effect Prediction of Proteins using RoseTTAFold'. Target MSAs, RF predicted PDBs and experimental values (csvs) are provided. Results published in paper are also provided.
View article: Mutation Effect Prediction of Proteins using RoseTTAFold
Mutation Effect Prediction of Proteins using RoseTTAFold Open
Deep mutational scanning datasets used for 'Mutation Effect Prediction of Proteins using RoseTTAFold'. Target MSAs, RF predicted PDBs and experimental values (csvs) are provided. Results published and referenced in paper are also provided.
View article: Mutation Effect Prediction of Proteins using RoseTTAFold
Mutation Effect Prediction of Proteins using RoseTTAFold Open
Deep mutational scanning datasets used for 'Mutation Effect Prediction of Proteins using RoseTTAFold'. Target MSAs, RF predicted PDBs and experimental values (csvs) are provided. Results published and referenced in paper are also provided.