Robust deep learning–based protein sequence design using ProteinMPNN

J Dauparas, I Anishchenko, N Bennett, H Bai… - Science, 2022 - science.org
Although deep learning has revolutionized protein structure prediction, almost all
experimentally characterized de novo protein designs have been generated using …

Chemoenzymatic semisynthesis of proteins

RE Thompson, TW Muir - Chemical reviews, 2019 - ACS Publications
Protein semisynthesis—defined herein as the assembly of a protein from a combination of
synthetic and recombinant fragments—is a burgeoning field of chemical biology that has …

Scaffolding protein functional sites using deep learning

J Wang, S Lisanza, D Juergens, D Tischer, JL Watson… - Science, 2022 - science.org
The binding and catalytic functions of proteins are generally mediated by a small number of
functional residues held in place by the overall protein structure. Here, we describe deep …

Generalized biomolecular modeling and design with RoseTTAFold All-Atom

R Krishna, J Wang, W Ahern, P Sturmfels, P Venkatesh… - Science, 2024 - science.org
Deep-learning methods have revolutionized protein structure prediction and design but are
presently limited to protein-only systems. We describe RoseTTAFold All-Atom (RFAA), which …

Hallucinating symmetric protein assemblies

BIM Wicky, LF Milles, A Courbet, RJ Ragotte… - Science, 2022 - science.org
Deep learning generative approaches provide an opportunity to broadly explore protein
structure space beyond the sequences and structures of natural proteins. Here, we use deep …

Improving protein expression, stability, and function with ProteinMPNN

KH Sumida, R Núñez-Franco, I Kalvet… - Journal of the …, 2024 - ACS Publications
Natural proteins are highly optimized for function but are often difficult to produce at a scale
suitable for biotechnological applications due to poor expression in heterologous systems …

Multistate and functional protein design using RoseTTAFold sequence space diffusion

SL Lisanza, JM Gershon, SWK Tipps, JN Sims… - Nature …, 2024 - nature.com
Protein denoising diffusion probabilistic models are used for the de novo generation of
protein backbones but are limited in their ability to guide generation of proteins with …

De novo design of allosterically switchable protein assemblies

A Pillai, A Idris, A Philomin, C Weidle, R Skotheim… - Nature, 2024 - nature.com
Allosteric modulation of protein function, wherein the binding of an effector to a protein
triggers conformational changes at distant functional sites, plays a central part in the control …

Binding and sensing diverse small molecules using shape-complementary pseudocycles

L An, M Said, L Tran, S Majumder, I Goreshnik, GR Lee… - Science, 2024 - science.org
We describe an approach for designing high-affinity small molecule–binding proteins poised
for downstream sensing. We use deep learning–generated pseudocycles with repeating …

Reconfigurable asymmetric protein assemblies through implicit negative design

DD Sahtoe, F Praetorius, A Courbet, Y Hsia, BIM Wicky… - Science, 2022 - science.org
Asymmetric multiprotein complexes that undergo subunit exchange play central roles in
biology but present a challenge for design because the components must not only contain …