William Sheffler

Programmable De Novo Design of Mesoporous Protein Crystal Frameworks

This paper presents a modular strategy to design programmable, highly porous protein crystals with tunable architectures and composition, enabling applications in catalysis and biomedicine.

Bond-centric modular design of protein assemblies

The paper introduces a modular bond-centric design approach for protein assemblies, demonstrating the successful creation of multiple polyhedral cages, 2D arrays, and 3D lattices with high success rates.

De novo design of inducibly assembling multi-component filaments

This paper computationally designs multi-component protein filaments that assemble into ordered fibers, validated by cryoEM, and shows regulation via phosphorylation.

Nucleation limited assembly and polarized growth of a de novo-designed allosterically modulatable protein filament

This paper designs a tunable protein filament that assembles in response to a peptide ligand and demonstrates its polarized growth and nucleation mechanisms.

Accurate Computational Design of 3D Protein Crystals

This paper designs 3D protein crystals with specified lattice architectures using computational methods, achieving atomic accuracy and demonstrating successful experimental validation.

Broadly applicable and accurate protein design by integrating structure prediction networks and diffusion generative models

Fine-tuning RoseTTAFold as a diffusion denoiser gives RFdiffusion, a general protein backbone generator; a designed influenza haemagglutinin binder matched its model by cryo-EM.

Computational design of nanoscale rotational mechanics in de novo protein assemblies

This paper computationally designs self-assembling protein rotary machines that sample internal rotational degrees of freedom based on energy landscapes.

Design of Biologically Active Binary Protein 2D Materials

The paper designs binary 2D protein co-assemblies that form ordered, biologically active materials with potential therapeutic applications.

Tailored Design of Protein Nanoparticle Scaffolds for Multivalent Presentation of Viral Glycoprotein Antigens

Designed trimers matched to viral glycoprotein termini yielded tetrahedral, octahedral and icosahedral nanoparticles with cryo-EM-verified structures that display native-like HIV Env, influenza HA and RSV F.