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...

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...

Ligand Binding Sites

Ligand Binding Sites

Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...

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...

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...

You might also read

Related Articles

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

Sort by

Same author

EMReady2: improvement of cryo-EM and cryo-ET maps by local quality-aware deep learning with Mamba.

Nature communications·2026

Same author

Structural atlas of the intact jumbo phage phiKZ.

Nature communications·2026

Same author

MetalKB: Predicting Metal Binding Sites on Proteins with a Knowledge-Based Graph Framework.

Journal of chemical information and modeling·2026

Same author

Topology-Informed Design of Circularly Locked DNAzymes Enables Orthogonally Controlled Gene Regulation.

Journal of the American Chemical Society·2026

Same author

EMProt improves structure determination from cryo-EM maps.

Nature structural & molecular biology·2025

Same author

Protein-Ligand Structure Prediction by Template-Guided Ensemble Docking Strategy.

Proteins·2025

Search research articles

Related Experiment Video

Updated: Aug 22, 2025

Application of I TASSER, trRosetta, UCSF Chimera, HADDOCK server, and HEX loria for De Novo and In Silico Design of Proteins

Application of I TASSER, trRosetta, UCSF Chimera, HADDOCK server, and HEX loria for De Novo and In Silico Design of Proteins

Published on: July 8, 2025

Holo Protein Conformation Generation from Apo Structures by Ligand Binding Site Refinement.

Jinze Zhang¹, Hao Li¹, Xuejun Zhao¹

¹School of Physics, Huazhong University of Science and Technology, Wuhan430074, Hubei, P. R. China.

Journal of Chemical Information and Modeling

|November 7, 2022

Summary

This study presents a new method to generate holo-like protein structures from apo structures. This approach refines ligand binding sites, improving drug discovery by providing more accurate protein conformations.

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

Author Spotlight: Exploring Cellular Processes by Modeling Ligands in Cryo-EM Maps

Author Spotlight: Exploring Cellular Processes by Modeling Ligands in Cryo-EM Maps

Published on: July 19, 2024

Related Experiment Videos

Last Updated: Aug 22, 2025

Application of I TASSER, trRosetta, UCSF Chimera, HADDOCK server, and HEX loria for De Novo and In Silico Design of Proteins

Application of I TASSER, trRosetta, UCSF Chimera, HADDOCK server, and HEX loria for De Novo and In Silico Design of Proteins

Published on: July 8, 2025

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

Author Spotlight: Exploring Cellular Processes by Modeling Ligands in Cryo-EM Maps

Author Spotlight: Exploring Cellular Processes by Modeling Ligands in Cryo-EM Maps

Published on: July 19, 2024

Area of Science:

Computational chemistry
Structural biology
Drug discovery

Background:

Structure-based drug design relies on accurate protein structures.
Holo protein structures with defined binding sites are superior to apo structures for drug discovery.
Obtaining holo structures can be challenging, necessitating methods to derive holo-like conformations from apo structures.

Purpose of the Study:

To develop a robust method for generating holo-like protein structures from apo structures.
To refine ligand binding sites in apo structures using information from low-homology holo templates.
To assess the effectiveness of the generated holo-like structures in drug discovery applications.

Main Methods:

Ligand binding site refinement of apo protein structures.
Utilizing restraints derived from holo templates with low sequence homology.
Testing the method on a dataset of 32 proteins from the DUD-E dataset.
Comparing the refined structures with apo structures and other methods.

Main Results:

Successfully refined apo structures towards holo conformations for 23 out of 32 proteins.
Reduced the average all-heavy-atom Root Mean Square Deviation (RMSD) of binding site residues by 0.48 Å.
Improved binding site RMSD for 14 out of 19 proteins with significant conformational changes.
Demonstrated advantages in ligand binding mode prediction and virtual screening compared to apo structures.

Conclusions:

The developed method is effective in recovering holo-like protein conformations from apo structures.
The refined structures enhance the accuracy of ligand binding predictions and virtual screening.
This approach offers a valuable tool for structure-based drug discovery when holo structures are unavailable.