Tag

De Novo Design

All articles tagged with #de novo design

science7 days ago•19 min saved

Single-building-block design yields versatile quasisymmetric protein nanocages

Researchers demonstrate de novo design of large, quasisymmetric protein cages built from a single building block. By leveraging spontaneous symmetry breaking, a parametric cage-design framework, and RoseTTAFold diffusion modelling (with ProteinMPNN for sequence design), they generate 3 ≤ T ≤ 36 cages containing 180–2,160 subunits and diameters from 68 to 220 nm. Cryo-EM confirms the structures and shows symmetry breaking across non-equivalent subunit positions, expanding the design space for one-component cages with potential for delivering biologics at large internal volumes.

via Nature|

#cryo-em #de-novo-design #protein-nanocages

science7 days ago•18 min saved

Designer miniproteins target GPCRs with high precision

Nature reports computational de novo design of miniproteins that bind G protein-coupled receptors (GPCRs) with high affinity, enabling both agonists for itch/pain receptors and antagonists for cancer, metabolic disorders, and migraine. Cryo-EM structures of five receptor–miniprotein complexes closely match the design models, validating the approach, and a designed chemokine receptor antagonist mobilizes hematopoietic stem and progenitor cells in vivo with fewer adverse effects than a clinically used drug.

via Nature|

#cryo-em #de-novo-design #gpcr

science8 days ago•25 min saved

Programmable quasisymmetric protein cages from two complementary building blocks

Nature reports a computational design strategy using geometric frustration to create two-component, quasisymmetric protein cages that assemble into sphere-like structures by embedding curvature-inducing pentagonal defects. By pairing complementary trimeric and dimeric blocks, the authors programmably control cage size from ~40 nm to >200 nm and mass from 2 to >50 MDa, comparable to viral capsids. The cages are functionalized for ribonucleoprotein cargo loading and cellular uptake, enabling studies of cargo delivery and size-dependent diffusion in cells. Data and code are publicly available (Zenodo, GitHub), underscoring a new route for biologics delivery and cell biology tools.

via Nature|

#cryo-em #de-novo-design #protein-cages

science-and-technology2 years ago•5 min saved

AI-Driven De Novo Design of High-Affinity Binders for Bioactive Peptides and Proteins

Researchers have developed a method for de novo protein design to generate high-affinity binders for bioactive helical peptides. By combining parametric generation and deep learning-based techniques, they were able to design binders with picomolar affinity to helical peptide targets. These designed binding proteins can be used for sensitive detection and clinical management of diseases. The method also enables the construction of protein biosensors. This represents a significant advancement in the field of protein design without the need for experimental optimization.

via Nature.com|

#bioactive-helical-peptides #de-novo-design #high-affinity-binders