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

Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

9.0K
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
9.0K
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

2.7K
2.7K
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

3.1K
3.1K
Conserved Binding Sites01:49

Conserved Binding Sites

5.2K
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...
5.2K
Conserved Binding Sites01:49

Conserved Binding Sites

2.0K
2.0K
¹H NMR of Conformationally Flexible Molecules: Temporal Resolution00:52

¹H NMR of Conformationally Flexible Molecules: Temporal Resolution

1.3K
At room temperature, the chair conformer of cyclohexane undergoes rapid ring flipping between two equivalent chair conformers at a rate of approximately 105 times per second. These two chair conformers are in equilibrium. The rapid ring flipping results in the interconversion of the axial proton to an equatorial proton and an equatorial to the axial proton. Such interconversions are too rapid and cannot be detected on the NMR timescale. Hence, the NMR spectrometer cannot distinguish between the...
1.3K

You might also read

Related Articles

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

Sort by
Same author

Active Learning FEP Using 3D-QSAR for Prioritizing Bioisosteres in Medicinal Chemistry.

ACS medicinal chemistry letters·2025
Same author

Adaptive Lambda Scheduling: A Method for Computational Efficiency in Free Energy Perturbation Simulations.

Journal of chemical information and modeling·2025
Same author

BAY-069, a Novel (Trifluoromethyl)pyrimidinedione-Based BCAT1/2 Inhibitor and Chemical Probe.

Journal of medicinal chemistry·2022
Same author

Atomistic mechanisms of human TRPA1 activation by electrophile irritants through molecular dynamics simulation and mutual information analysis.

Scientific reports·2022
Same author

Conformational Searching with Quantum Mechanics.

Methods in molecular biology (Clifton, N.J.)·2020
Same author

Conformational ensemble comparison for small molecules in drug discovery.

Journal of computer-aided molecular design·2018

Related Experiment Video

Updated: Feb 17, 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

1.3K

Bioactive focus in conformational ensembles: a pluralistic approach.

Matthew Habgood1

  • 1Evotec (UK) Ltd., 114 Innovation Drive, Milton Park, Abingdon, Oxfordshire, OX14 4RZ, UK. matthew.habgood@evotec.com.

Journal of Computer-Aided Molecular Design
|December 1, 2017
PubMed
Summary

This study introduces a novel method for drug design, creating focused conformational ensembles by using multiple ranking factors beyond potential energy. This approach improves the selection of bioactive conformations for better drug targeting.

Keywords:
Cambridge Structural DatabaseComputer-aided drug designConformer generationConsensus approachMOE

More Related Videos

Investigating Protein Sequence-structure-dynamics Relationships with Bio3D-web
09:51

Investigating Protein Sequence-structure-dynamics Relationships with Bio3D-web

Published on: July 16, 2017

16.1K
Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
07:08

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues

Published on: July 14, 2015

7.7K

Related Experiment Videos

Last Updated: Feb 17, 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

1.3K
Investigating Protein Sequence-structure-dynamics Relationships with Bio3D-web
09:51

Investigating Protein Sequence-structure-dynamics Relationships with Bio3D-web

Published on: July 16, 2017

16.1K
Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
07:08

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues

Published on: July 14, 2015

7.7K

Area of Science:

  • Computational chemistry
  • Drug discovery
  • Structural biology

Background:

  • Generating conformational ensembles is crucial for drug design.
  • Traditional methods using only potential energy struggle to identify bioactive conformations.
  • A better approach is needed to focus ensembles on relevant molecular shapes.

Purpose of the Study:

  • To develop and test a new method for generating focused conformational ensembles.
  • To improve the identification of bioactive conformations for drug design.
  • To address the limitations of using potential energy alone for ranking conformations.

Main Methods:

  • Assigning multiple rankings to each conformation based on potential energy, solvation energy, hydrophobic/hydrophilic interactions, radius of gyration, and statistical potentials from the Cambridge Structural Database.
  • Assembling the best-ranked structures from each system into a new, focused ensemble.
  • Testing the approach on ensembles generated by Molecular Operating Environment's Low Mode Molecular Dynamics and Cambridge Crystallographic Data Centre's conformation generator.

Main Results:

  • The proposed pluralistic ranking approach successfully generates ensembles better focused on bioactive conformations.
  • This method enhances the discrimination between bioactive and non-bioactive conformations compared to energy-based methods alone.
  • The approach is validated using established computational tools in molecular modeling.

Conclusions:

  • A multi-faceted ranking strategy significantly improves the focus of conformational ensembles on bioactive states.
  • This computational approach offers a more effective way to select promising drug candidates in silico.
  • The findings have implications for advancing rational drug design and discovery pipelines.