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

12.7K
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:
12.7K
Ligand Binding Sites02:40

Ligand Binding Sites

12.6K
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...
12.6K
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

4.7K
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...
4.7K
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

2.3K
2.3K
Conserved Binding Sites01:49

Conserved Binding Sites

4.1K
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...
4.1K
Crystal Field Theory - Octahedral Complexes02:58

Crystal Field Theory - Octahedral Complexes

25.8K
Crystal Field Theory
To explain the observed behavior of transition metal complexes (such as colors), a model involving electrostatic interactions between the electrons from the ligands and the electrons in the unhybridized d orbitals of the central metal atom has been developed. This electrostatic model is crystal field theory (CFT). It helps to understand, interpret, and predict the colors, magnetic behavior, and some structures of coordination compounds of transition metals.
CFT focuses on...
25.8K

You might also read

Related Articles

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

Sort by
Same author

Emerging role of proteomics in advancing diagnosis, prognosis, and treatment of liver cancer.

Liver research (Beijing, China)·2026
Same author

Corrosion-assisted heterogeneous nucleation for CoNiFe layered double hydroxides toward high-current methanol oxidation.

Chemical communications (Cambridge, England)·2026
Same author

<i>Ab initio</i> molecular dynamics reveal multiple hydroxyl-driven degradation pathways of imidazolium-based anion exchange membranes.

Physical chemistry chemical physics : PCCP·2026
Same author

Exploring the effectiveness and sequence of brain local treatment combined with thoracic surgery in non-small cell lung cancer patients with brain oligometastasis.

Translational lung cancer research·2026
Same author

Structural diversity of metatranscriptomic cellulases drives lignocellulose bioconversion by black soldier fly.

Bioresource technology·2026
Same author

miR-34 regulates cuticle pigmentation by targeting <i>Bm-iAANAT</i> and <i>Bmserpin3</i> in <i>Bombyx mori</i>.

RNA biology·2026

Related Experiment Video

Updated: May 15, 2025

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
10:29

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

67

Applying Absolute Free Energy Perturbation Molecular Dynamics to Diffusively Binding Ligands.

Xavier E Laracuente1, Bryan M Delfing1, Xingyu Luo1

  • 1School of Systems Biology, George Mason University, Manassas, Virginia 20110, United States.

Journal of Chemical Theory and Computation
|April 7, 2025
PubMed
Summary

We developed a new simulation protocol to calculate binding free energy for difficult protein-ligand interactions. This method accurately predicted the binding affinity and mechanism of a peptide ligand, minNLS, to importin-α.

More Related Videos

Determination of Protein-ligand Interactions Using Differential Scanning Fluorimetry
13:26

Determination of Protein-ligand Interactions Using Differential Scanning Fluorimetry

Published on: September 13, 2014

61.5K
Analyzing Protein Architectures and Protein-Ligand Complexes by Integrative Structural Mass Spectrometry
07:33

Analyzing Protein Architectures and Protein-Ligand Complexes by Integrative Structural Mass Spectrometry

Published on: October 15, 2018

14.1K

Related Experiment Videos

Last Updated: May 15, 2025

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
10:29

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

67
Determination of Protein-ligand Interactions Using Differential Scanning Fluorimetry
13:26

Determination of Protein-ligand Interactions Using Differential Scanning Fluorimetry

Published on: September 13, 2014

61.5K
Analyzing Protein Architectures and Protein-Ligand Complexes by Integrative Structural Mass Spectrometry
07:33

Analyzing Protein Architectures and Protein-Ligand Complexes by Integrative Structural Mass Spectrometry

Published on: October 15, 2018

14.1K

Area of Science:

  • Computational Chemistry
  • Structural Biology
  • Biophysics

Background:

  • Ligands that bind diffusively to proteins pose challenges for traditional free energy perturbation (FEP) simulations.
  • Understanding these binding mechanisms is crucial for drug discovery and molecular biology.

Purpose of the Study:

  • To develop and validate an advanced FEP protocol for calculating binding free energy and mechanism of diffusively binding ligands.
  • To investigate the binding of a minNLS peptide to importin-α, a system with no well-defined binding poses.

Main Methods:

  • Developed an absolute free energy perturbation (FEP) protocol integrating all-atom molecular dynamics, replica exchange with solute tempering (REST) enhanced sampling, and spherical harmonic restraints.
  • Applied the FEP/REST protocol to simulate the binding of the minNLS peptide (KKPK) to importin-α.
  • Analyzed simulation data to determine binding free energy, binding mechanism, and structural ensemble of the bound ligand.

Main Results:

  • The FEP/REST protocol successfully computed a converged binding free energy estimate for minNLS.
  • Demonstrated that minNLS binds to importin-α with moderate affinity via a unique, purely entropic mechanism.
  • Identified the release of water from charged amino acid solvation shells as the primary driver of favorable binding entropy.
  • Characterized the distribution of bound structures, interactions, and binding sites on importin-α.

Conclusions:

  • The developed FEP/REST protocol is effective for simulating diffusively binding ligands.
  • The binding of minNLS to importin-α is primarily driven by favorable entropic contributions, particularly water release.
  • This study provides insights into unusual binding mechanisms and offers a robust computational approach for challenging ligand-protein systems.