Protein design articles from across Nature Portfolio

A set of 20 computational metrics was evaluated to determine whether they could predict the functionality of synthetic enzyme sequences produced by generative protein models, resulting in the development of a computational filter, COMPSS, that increased experimental success rates by 50–150%, tested in over 500 natural and AI-generated enzymes.

Peptide vaccines use antigenic peptide fragments to induce an immune response but are problematic because of the short half-life of peptides. A study now reports thioamide substitution in the peptide backbone as a strategy to enhance resistance to proteolysis and promote binding to the MHC I complex for T cell activation.

Metrics that predict the success of folding and the activity of designed protein sequences are developed and experimentally validated.

Here, the authors show that biomolecular condensates can enhance enzymatic rates by creating distinct solvent environments compared to the surrounding solution, and this emergent property can manifest within assemblies as small as nanometers.

Asparaginyl ligases have been utilized as valuable tools for protein engineering, such as through site-specific bioconjugation or surface modification, however, their application is limited due to time-consuming preparation processes and unstable activities. Here, the authors develop a truncated protein ligase OaAEP1-C247A-aa55-351 from an OaAEP1-C247A mutant, which simplifies the preparation steps, tolerates a wider pH range, and enhances the catalytic activities by using efficient recognition and nucleophile motifs.

Citrate synthase from the cyanobacterium Synechococcus elongatus is shown to self-assemble into Sierpiński triangles, a finding that opens up the possibility that other naturally occurring molecular-scale fractals exist.

Recent combinations of structure-based and sequence-based calculations and machine learning tools have dramatically improved protein engineering and design. Although designing complex protein structures remains challenging, these methods have enabled the design of therapeutically relevant activities, including vaccine antigens, antivirals and drug-delivery nano-vehicles.

A set of 20 computational metrics was evaluated to determine whether they could predict the functionality of synthetic enzyme sequences produced by generative protein models, resulting in the development of a computational filter, COMPSS, that increased experimental success rates by 50–150%, tested in over 500 natural and AI-generated enzymes.

Peptide vaccines use antigenic peptide fragments to induce an immune response but are problematic because of the short half-life of peptides. A study now reports thioamide substitution in the peptide backbone as a strategy to enhance resistance to proteolysis and promote binding to the MHC I complex for T cell activation.

An article in Nature describes regular, modular protein building blocks that can be combined — following a standard blueprint — into a variety of architectures.

Expansion of the genetic code can enable precise manipulation of proteins through selective functionalization of specific residues. Now, control of tryptophan interactions in proteins can be established by encoding of a vinyl-caged tryptophan analogue that can be selectively decaged to rescue protein activity.

Reprogramming of the genetic code allows the synthesis of proteins using new building blocks, thus opening the door to the development of a wider variety of medicines and biocatalysts; however, it is currently limited to α-amino acids. A new study has now reported the incorporation of β-linked and α,α-disubstituted monomers into a ribosome-synthesized protein.