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

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...

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...

Ligand Binding and Linkage

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence the...

Ligand Binding and Linkage

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence the...

The Equilibrium Binding Constant and Binding Strength

The Equilibrium Binding Constant and Binding Strength

The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium:

Complexometric Titration: Ligands

Complexometric Titration: Ligands

Different monodentate and polydentate ligands are used as complexing agents in complexometric titration reactions. The formation of complexes by mono- and bidentate ligands involves two or more intermediate steps, limiting their use as complexing agents. In comparison, polydentate ligands can form complexes with metal ions in a single-step process, facilitating sharper end points. This means polydentate ligands, such as amino carboxylic acid derivatives, are most commonly employed in...

You might also read

Related Articles

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

Sort by

Same author

Prediction of pre- and postfusion conformations of class I fusion proteins with AlphaFold2.

PloS one·2026

Same author

Structure-guided compound prioritization strategy for virtual screening identifies putative binders for the nuclear receptor LRH-1.

bioRxiv : the preprint server for biology·2026

Same author

Profiling the CFTR Variant Selectivity and Off-Target Interactions of VX-121.

bioRxiv : the preprint server for biology·2026

Same author

EGFR S442 ectodomain mutation confers cetuximab resistance that can be overcome by ERBB2 blockade with trastuzumab-deruxtecan.

Cancer letters·2026

Same author

Lanthipeptide structure prediction and design with Rosetta.

Methods in enzymology·2026

Same author

VUStruct: A compute pipeline for high throughput and personalized structural biology.

PLoS computational biology·2026

Same journal

Analysis of strength degradation of coal and rock masses and stability of mined areas under long term immersion environment.

PloS one·2026

Same journal

Biogenic Silver-Selenium nanocomposite with anticancer activity and potent efficacy against vancomycin-resistant Staphylococcus aureus.

PloS one·2026

Same journal

Preparation and physicochemical characterization of a biodegradable chitosan/carboxymethyl cellulose hydrogel synthesized in NaOH/urea medium.

PloS one·2026

Same journal

Action-guilt, survivor-guilt, and depression in combat-related PTSD.

PloS one·2026

Same journal

Explainable machine learning for predicting activities of daily living at discharge in stroke patients: A retrospective study using SHAP interpretability.

PloS one·2026

Same journal

Deep learning based two-way feature depiction model for brain tumor detection.

PloS one·2026

See all related articles

Search research articles

Related Experiment Video

Updated: May 9, 2026

Modeling Ligands into Maps Derived from Electron Cryomicroscopy

Modeling Ligands into Maps Derived from Electron Cryomicroscopy

Published on: July 19, 2024

Towards ligand docking including explicit interface water molecules.

Gordon Lemmon¹, Jens Meiler

¹Center for Structural Biology, Vanderbilt University, Nashville, Tennessee, United States of America.

|July 11, 2013

Summary

This summary is machine-generated.

Adding explicit water molecules to docking simulations significantly enhances the accuracy of predicting protein-ligand interactions. This improved molecular docking approach aids in correctly modeling complex structures, especially for drug discovery.

More Related Videos

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis

Published on: June 20, 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

Related Experiment Videos

Last Updated: May 9, 2026

Modeling Ligands into Maps Derived from Electron Cryomicroscopy

Modeling Ligands into Maps Derived from Electron Cryomicroscopy

Published on: July 19, 2024

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis

Published on: June 20, 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

Area of Science:

Computational Biology
Structural Biology
Drug Discovery

Background:

Molecular docking predicts protein-ligand interactions at atomic detail, but current algorithms like RosettaLigand sometimes fail to identify correct complex structures.
Accurate prediction of protein-ligand binding poses is crucial for rational drug design and understanding biological mechanisms.

Purpose of the Study:

To investigate whether incorporating explicit interface water molecules into docking simulations can improve the accuracy of RosettaLigand in predicting correct protein-ligand complex structures.
To evaluate the effectiveness of both protein-centric and ligand-centric water docking strategies.

Main Methods:

Simultaneous docking of explicit interface water molecules with small molecule ligands and protein targets using the RosettaLigand algorithm.
Protein-centric water docking: waters are fixed relative to the protein binding site.
Ligand-centric water docking: waters move with the ligand during the docking process.

Main Results:

Including a single critical interface water molecule improved HIV-1 protease/protease inhibitor placement accuracy by a ratio of 9:1 in protein-centric docking.
Ligand-centric water docking recovered up to 56% of previously failed docking studies across a diverse benchmark dataset (CSAR).
Simultaneous docking of explicit interface water molecules significantly enhances Rosetta's ability to differentiate correct from incorrect ligand poses.

Conclusions:

Explicit interface water molecules are critical for accurate molecular docking and should be incorporated into simulation protocols.
Both protein-centric and ligand-centric water docking strategies offer substantial improvements in predicting protein-ligand complex structures.
This enhanced docking approach holds significant promise for improving drug discovery pipelines by increasing the success rate of virtual screening and lead optimization.