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Protein Engineering

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LevSeq: Rapid Generation of Sequence-Function Data for Directed Evolution and Machine Learning.

ACS synthetic biology
Sequence-function data provides valuable information about the protein functional landscape but is rarely obtained during directed evolution campaigns. Here, we present Long-read every variant Sequencing (LevSeq), a pipeline that combines a dual barc...

A synthetic protein-level neural network in mammalian cells.

Science (New York, N.Y.)
Artificial neural networks provide a powerful paradigm for nonbiological information processing. To understand whether similar principles could enable computation within living cells, we combined de novo-designed protein heterodimers and engineered v...

Accelerated enzyme engineering by machine-learning guided cell-free expression.

Nature communications
Enzyme engineering is limited by the challenge of rapidly generating and using large datasets of sequence-function relationships for predictive design. To address this challenge, we develop a machine learning (ML)-guided platform that integrates cell...

Tailoring industrial enzymes for thermostability and activity evolution by the machine learning-based iCASE strategy.

Nature communications
The pursuit of obtaining enzymes with high activity and stability remains a grail in enzyme evolution due to the stability-activity trade-off. Here, we develop an isothermal compressibility-assisted dynamic squeezing index perturbation engineering (i...

Biochemical and Computational Characterization of Haloalkane Dehalogenase Variants Designed by Generative AI: Accelerating the S2 Step.

Journal of the American Chemical Society
Generative artificial intelligence (AI) models trained on natural protein sequences have been used to design functional enzymes. However, their ability to predict individual reaction steps in enzyme catalysis remains unclear, limiting the potential u...

Data and AI-driven synthetic binding protein discovery.

Trends in pharmacological sciences
Synthetic binding proteins (SBPs) are a class of protein binders that are artificially created and do not exist naturally. Their broad applications in tackling challenges of research, diagnostics, and therapeutics have garnered significant interest. ...

Self-supervised machine learning methods for protein design improve sampling but not the identification of high-fitness variants.

Science advances
Machine learning (ML) is changing the world of computational protein design, with data-driven methods surpassing biophysical-based methods in experimental success. However, they are most often reported as case studies, lack integration and standardiz...

Deep Learning-Assisted Discovery of Protein Entangling Motifs.

Biomacromolecules
Natural topological proteins exhibit unique properties including enhanced stability, controlled quaternary structures, and dynamic switching properties, highlighting topology as a unique dimension in protein engineering. Although artificial design an...

Long-Range Electrostatics in Serine Proteases: Machine Learning-Driven Reaction Sampling Yields Insights for Enzyme Design.

Journal of chemical information and modeling
Computational enzyme design is a promising technique for producing novel enzymes for industrial and clinical needs. A key challenge that this technique faces is to consistently achieve the desired activity. Fundamental studies of natural enzymes reve...

Unveiling the new chapter in nanobody engineering: advances in traditional construction and AI-driven optimization.

Journal of nanobiotechnology
Nanobodies (Nbs), miniature antibodies consisting solely of the variable region of heavy chains, exhibit unique properties such as small size, high stability, and strong specificity, making them highly promising for disease diagnosis and treatment. T...