Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Protein Folding

Protein Folding

Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...

Protein Organization

Protein Organization

Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence....

Conservation of Protein Domains Over Different Proteins

Conservation of Protein Domains Over Different Proteins

Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...

Molecular Chaperones and Protein Folding

Molecular Chaperones and Protein Folding

The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...

Conserved Binding Sites

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...

Protein and Protein Structure

Protein and Protein Structure

Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Efficient generation of epitope-targeted antibodies with Germinal.

Nature biotechnology·2026

Same author

Genome modelling and design across all domains of life with Evo 2.

Nature·2026

Same author

Rapid directed evolution guided by protein language models and epistatic interactions.

Science (New York, N.Y.)·2026

Same author

Development of ACE2-tropic-betacoronavirus therapeutics for future pandemic preparedness.

Nature communications·2025

Same author

Semantic design of functional de novo genes from a genomic language model.

Nature·2025

Same author

Efficient generation of epitope-targeted <i>de novo</i> antibodies with Germinal.

bioRxiv : the preprint server for biology·2025

Search research articles

Related Experiment Video

Updated: Jul 6, 2025

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions

Published on: January 26, 2024

Inverse folding of protein complexes with a structure-informed language model enables unsupervised antibody

Varun R Shanker^1,2,3, Theodora U J Bruun^2,3,4, Brian L Hie^3,4

¹Stanford Biophysics Program, Stanford University School of Medicine, Stanford, CA 94305, USA.

Biorxiv : the Preprint Server for Biology

|January 8, 2024

Summary

Protein language models augmented with 3D structure data can guide protein evolution. This inverse folding approach significantly improves antibody function against SARS-CoV-2 variants.

More Related Videos

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules

Published on: July 25, 2013

A Protocol for Computer-Based Protein Structure and Function Prediction

A Protocol for Computer-Based Protein Structure and Function Prediction

Published on: November 3, 2011

Related Experiment Videos

Last Updated: Jul 6, 2025

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions

Published on: January 26, 2024

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules

Published on: July 25, 2013

A Protocol for Computer-Based Protein Structure and Function Prediction

A Protocol for Computer-Based Protein Structure and Function Prediction

Published on: November 3, 2011

Area of Science:

Computational biology
Protein engineering
Machine learning in drug discovery

Background:

Protein function is dictated by 3D structure, not just sequence.
Existing protein language models primarily use sequence data.
3D structural information is crucial for understanding protein activity and evolution.

Approach:

Developed a protein language model incorporating 3D backbone coordinates.
Trained the model on the inverse folding problem for structure-based sequence optimization.
Applied the model to guide the evolution of therapeutic antibodies.

Key Points:

Inverse folding serves as an unsupervised, structure-based optimization strategy.
The method generalizes to multimeric protein complexes, learning binding and epistasis.
Achieved significant improvements in antibody neutralization and affinity against SARS-CoV-2 variants BQ.1.1 and XBB.1.5.

Conclusions:

This structure-guided protein language model enhances protein function without task-specific training.
Inverse folding demonstrates leading experimental success rates compared to other ML-guided directed evolution methods.
The approach offers a powerful tool for engineering diverse proteins and therapeutic antibodies.