Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

The Equilibrium Binding Constant and Binding Strength02:18

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:
The Equilibrium Binding Constant and Binding Strength02:18

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:
Protein-Drug Binding: Determination Methods01:22

Protein-Drug Binding: Determination Methods

Determining protein-drug binding can be achieved through indirect and direct methods, each providing valuable insights into the interaction between proteins and drugs.
Indirect methods involve isolating the bound drug from its free form in biological samples such as blood, serum, or plasma. These techniques aim to measure the percentage of drugs bound to proteins. Equilibrium dialysis is a commonly used method where the free drug concentration at equilibrium is measured by separating the bound...
Ligand Binding Sites02:40

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 Sites02:40

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...
Calculating Standard Free Energy Changes02:49

Calculating Standard Free Energy Changes

The free energy change for a reaction that occurs under the standard conditions of 1 bar pressure and at 298 K is called the standard free energy change. Since free energy is a state function, its value depends only on the conditions of the initial and final states of the system. A convenient and common approach to the calculation of free energy changes for physical and chemical reactions is by use of widely available compilations of standard state thermodynamic data. One method involves the...

You might also read

Related Articles

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

Sort by
Same author

Correction to "Structural Dynamics and Catalytic Mechanism of ATP13A2 (PARK9) from Simulations".

The journal of physical chemistry. B·2026
Same author

Linking biochemical and cellular efficacy of MERS coronavirus main protease inhibitors.

ACS pharmacology & translational science·2026
Same author

Bridging between Structure-Based and Data-Driven Affinity Prediction.

Journal of chemical information and modeling·2026
Same author

Two-Dimensional Visual Experimental Investigation of Interlayer Effects on Thermal Recovery in Bottom-Water Heavy Oil Reservoirs.

ACS omega·2026
Same author

Time-Series Analysis of Pregnancy and Childbirth Effects on Pelvic Floor Muscle Electrophysiology and Morphology in Rats.

International urogynecology journal·2026
Same author

HB reduces inflammation in HUVECs via the Nrf2/HO-1 axis by inhabiting apoptosis and oxidative stress.

Scientific reports·2026

Related Experiment Video

Updated: May 22, 2026

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
08:49

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

Published on: June 20, 2025

Large-Scale Collaborative Assessment of Binding Free Energy Calculations for Drug Discovery Using OpenFE.

Hannah M Baumann1, Joshua T Horton1, Michael M Henry1,2

  • 1Open Free Energy, Open Molecular Software Foundation, Davis, California 95616, United States.

Journal of Chemical Information and Modeling
|May 21, 2026
PubMed
Summary

This study validates the Open Free Energy (OpenFE) protocol for calculating relative binding free energy (RBFE) in drug discovery. The open-source tool shows industrial readiness, achieving accuracy comparable to commercial solutions.

More Related Videos

Nano-Differential Scanning Fluorimetry for Screening in Fragment-based Lead Discovery
06:26

Nano-Differential Scanning Fluorimetry for Screening in Fragment-based Lead Discovery

Published on: May 16, 2021

A Bilingual Computational Workflow for Identifying Potential PLK1 Inhibitors in American Sign Language and English
14:34

A Bilingual Computational Workflow for Identifying Potential PLK1 Inhibitors in American Sign Language and English

Published on: April 3, 2026

Related Experiment Videos

Last Updated: May 22, 2026

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
08:49

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

Published on: June 20, 2025

Nano-Differential Scanning Fluorimetry for Screening in Fragment-based Lead Discovery
06:26

Nano-Differential Scanning Fluorimetry for Screening in Fragment-based Lead Discovery

Published on: May 16, 2021

A Bilingual Computational Workflow for Identifying Potential PLK1 Inhibitors in American Sign Language and English
14:34

A Bilingual Computational Workflow for Identifying Potential PLK1 Inhibitors in American Sign Language and English

Published on: April 3, 2026

Area of Science:

  • Computational chemistry
  • Molecular modeling
  • Drug discovery

Background:

  • Accurate measurement of compound binding affinities is crucial for pharmaceutical development.
  • Physics-based in silico methods, especially alchemical free energy calculations, are gold-standard tools for estimating binding affinity changes.
  • A large-scale collaborative assessment was conducted to evaluate a specific relative binding free energy (RBFE) protocol.

Purpose of the Study:

  • To assess the performance of an open-source, MIT-licensed RBFE protocol from the Open Free Energy (OpenFE) ecosystem.
  • To evaluate the protocol's accuracy and robustness across diverse public and private datasets.
  • To determine the readiness of the OpenFE protocol for large-scale industrial applications in drug discovery.

Main Methods:

  • Evaluation of an open-source RBFE protocol (OpenFE) using both public and blinded private datasets.
  • Analysis of over 1,700 ligands across 58 public and 37 private systems.
  • Calculation of weighted Root Mean Square Error (RMSE) to quantify accuracy.

Main Results:

  • The OpenFE protocol achieved a weighted RMSE of 1.73 kcal/mol on the public dataset and 2.44 kcal/mol on the private dataset.
  • Sub-kcal/mol accuracy was reached in 10 public systems and 2 private systems, indicating system-dependent performance.
  • Performance was influenced by input quality and transformation type, with no single dominant error source.

Conclusions:

  • The OpenFE protocol demonstrates "out-of-the-box" accuracy approaching commercial solutions, making it suitable for industrial applications.
  • The protocol meets key industrial criteria including robust performance, reproducibility, throughput, and rapid convergence.
  • While ranking statistics are comparable to optimized commercial methods, further improvements in error statistics are possible.