Derek N. Woolfson

Exploring the Design Space of 310-helical Bundles using Non-canonical Amino Acids

This paper explores sequence constraints for de novo 310-helical bundles by mutating key residues in a designed peptide and assessing stability and functionality.

De novo designed bifunctional proteins for targeted protein degradation

This paper designs de novo bifunctional proteins for targeted protein degradation, demonstrating their ability to degrade BCL-xL in cells.

Expanding all-α-helical protein space through rational computational design

The paper designs de novo all-α-helical proteins using computational methods and validates their stability and structure.

Kinase-gated coincidence detection controls kinesin-driven lysosome transport

The paper identifies a phosphorylation-dependent gate on kinesin-1 activity mediated by KLC2 CTD, revealing a kinase-kinase code that regulates lysosome transport through adaptor binding and membrane cues.

Coiled-coil scaffolds for Targeted Protein Degradation

The paper demonstrates the use of coiled-coil scaffolds to enable targeted protein degradation by integrating target-binding and degradation motifs into single-polypeptide constructs.

Biomolecular condensation using de novo designed globular proteins

This paper designs globular proteins that drive biomolecular condensation and demonstrates their use in forming dynamic condensates in cells.

The WAVE complex forms linear arrays at negative membrane curvature to instruct lamellipodia formation.

This study shows the WAVE complex forms linear arrays at negative membrane curvature to instruct lamellipodia formation through in vivo biochemical approaches.

Rapid Assessment of Size, Shape, and Chemical Complementarity of Ligands for Computational Protein Design

The paper develops a computational method to design proteins that bind small molecules tightly and specifically, validated experimentally with X-ray crystallography and functional assays.

Kinesin-1 conformational dynamics are controlled by a cargo-sensitive TPR switch

This study shows that cargo-sensitive TPR switch in kinesin-1 controls its conformational dynamics by dislocating the TPR shoulder, promoting motor domain activation and microtubule binding.

The Protein Design Archive (PDA): insights from 40 years of protein design

The paper introduces the Protein Design Archive (PDA), a database of designed proteins, and analyzes its contents to show increasing complexity and diversity in protein design over time.

Tumbleweed: an artificial motor protein that walks along a DNA track

This paper introduces an artificial protein motor called Tumbleweed that walks directionally along a DNA track in response to ligand inputs.

Confinement and Catalysis Within De Novo Designed Peptide Barrels

This paper designs and characterizes peptide barrels that can bind and catalyze reactions between small molecules in solution.

De novo designed 3-helix bundle peptides and proteins with controlled topology and stability

This paper designs 3-helix bundle peptides and proteins with controlled topology and stability using computational methods and experimental validation.

De novo design of α-helical peptide channels with designer stoichiometry

This paper designs and characterizes α-helical peptide channels with specific stoichiometry and conductance properties through computational and experimental methods.

De novo design of parallel and antiparallel A3B3 heterohexameric alpha-helical barrels

This paper designs A3B3 heterohexameric alpha-helical barrels by controlling heptad register, showing that it affects helix orientation and using AlphaFold-Multimer for modeling.

Exchange, promiscuity, and orthogonality in de novo designed coiled-coil peptide assemblies

The paper develops a fluorescence-based assay to study peptide exchange in de novo coiled-coil assemblies and identifies strategies to improve orthogonality between oligomeric states.

Allosteric regulation of a molecular motor through de novo protein design

The paper engineers an allosteric switch in kinesin-1 motors using de novo peptides, showing increased transport in cells through conformational changes.

Maturation and conformational switching of a de novo designed phase-separating polypeptide

This study describes a de novo designed polypeptide that forms phase-separated droplets and fibers, showing droplet maturation into β-conformations similar to pathological assemblies.

An atlas of protein homo-oligomerization across domains of life

The paper predicts homo-oligomerization across four proteomes using AlphaFold2, finding that 50% of archaea, 45% of bacteria, and 20% of eukaryotes form homomers, with disease mutations enriched at interfaces.

CC + : A Searchable Database of Validated Coiled coils in PDB Structures and AlphaFold2 Models

The paper updates a database of coiled-coil structures from experimental data and AlphaFold2 models, enabling searches and analysis of coiled-coil assemblies and their sequence-structure relationships.

Assembling membraneless organelles from de novo designed proteins

The paper designs genetically encoded polypeptides that form membraneless organelles in E. coli and use them to co-compartmentalise a functional enzyme pair.

Rationally seeded computational protein design

This paper describes a computational method for designing -helical-barrel proteins with small molecule-binding channels, achieving high expression and structural accuracy in E. coli.

From peptides to proteins: coiled-coil tetramers to single-chain 4-helix bundles

The paper designs synthetic proteins by deriving sequence-to-structure rules from coiled-coil tetramers and validates them through experimental methods.

Constructing synthetic-protein assemblies from de novo designed 310 helices

This paper designs and characterizes synthetic protein assemblies composed of 310 helices, demonstrating their ability to form stable structures despite their rarity in natural proteins.

A designed high-affinity peptide that hijacks microtubule-based transport

The paper designs a high-affinity peptide (KinTag) that hijacks microtubule-based transport by binding KLCTPRs with nanomolar affinity, enhancing cargo transport efficiency.

De Novo Designed Peptide and Protein Hairpins Self-assemble into Sheets and Nanoparticles.

This paper designs peptides that self-assemble into nanoparticles or sheets based on disulfide bond placement, using computational modeling and microscopy.

Guiding biomolecular interactions in cells using de novo protein-protein interfaces

This paper designs de novo protein-protein interfaces to control biomolecular interactions in E. coli, demonstrating their ability to guide engineered protein-DNA interactions and modulate gene expression.