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

Predicting Molecular Geometry02:27

Predicting Molecular Geometry

46.2K
VSEPR Theory for Determination of Electron Pair Geometries
46.2K
Solvents01:12

Solvents

71.4K
A solvent is a substance, most often a liquid, that can dissolve other substances. Here, the substance being dissolved is called a solute. When a solvent and a solute combine, they form a solution - a homogenous mixture of both the solvent and the solute. Water is a universal biological solvent. Its polar structure allows it to dissolve many other polar compounds. The ability of water to dissolve is governed by a balance between water molecules binding to each other and binding to the solute.
A...
71.4K
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
Ligand Binding Sites02:40

Ligand Binding Sites

15.3K
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...
15.3K
Displacement Current01:19

Displacement Current

3.9K
Ampère's law, in its usual form, does not work in places where the current changes with time and is not steady. Thus, Maxwell suggested including an additional contribution, called the displacement current, Id, to the real conduction current I.
3.9K
Position and Displacement01:31

Position and Displacement

27.3K
The position of an object defines its location relative to a convenient frame of reference at any particular time. A frame of reference is an arbitrary set of axes from which the position and motion of an object are described. Earth is often used as a frame of reference, and we often describe the position of an object as it relates to stationary objects on Earth. For example, a rocket launch could be described in terms of the position of the rocket with respect to Earth as a whole. On the other...
27.3K

You might also read

Related Articles

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

Sort by
Same author

Integrating large scale genetic and clinical information to predict cases of heart failure.

Communications medicine·2025
Same author

Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications.

Nature communications·2024
Same author

Genome-wide association meta-analysis identifies risk loci for abdominal aortic aneurysm and highlights PCSK9 as a therapeutic target.

Nature genetics·2023
Same author

Genome-wide association study of thoracic aortic aneurysm and dissection in the Million Veteran Program.

Nature genetics·2023
Same author

Author Correction: The power of genetic diversity in genome-wide association studies of lipids.

Nature·2023
Same author

Identifying Potential Ligand Binding Sites on Glycogen Synthase Kinase 3 Using Atomistic Cosolvent Simulations.

ACS applied bio materials·2023

Related Experiment Video

Updated: Feb 16, 2026

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

2.4K

Predicting Displaceable Water Sites Using Mixed-Solvent Molecular Dynamics.

Sarah E Graham1, Richard D Smith1, Heather A Carlson1

  • 1Department of Biophysics and ‡Department of Medicinal Chemistry, College of Pharmacy, University of Michigan , 428 Church Street, Ann Arbor, Michigan 48109-1065, United States.

Journal of Chemical Information and Modeling
|December 30, 2017
PubMed
Summary

Mixed-solvent molecular dynamics (MixMD) identifies conserved and displaceable water sites in protein-ligand binding. This method predicts which water molecules are crucial for binding affinity and which can be displaced by ligands.

More Related Videos

Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes
09:42

Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes

Published on: January 16, 2016

9.4K
Analyzing Melts and Fluids from Ab Initio Molecular Dynamics Simulations with the UMD Package
06:37

Analyzing Melts and Fluids from Ab Initio Molecular Dynamics Simulations with the UMD Package

Published on: September 17, 2021

5.1K

Related Experiment Videos

Last Updated: Feb 16, 2026

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

2.4K
Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes
09:42

Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes

Published on: January 16, 2016

9.4K
Analyzing Melts and Fluids from Ab Initio Molecular Dynamics Simulations with the UMD Package
06:37

Analyzing Melts and Fluids from Ab Initio Molecular Dynamics Simulations with the UMD Package

Published on: September 17, 2021

5.1K

Area of Science:

  • Computational Chemistry
  • Structural Biology
  • Biophysics

Background:

  • Water molecules play a critical role in protein-ligand interactions, influencing binding affinity through displacement or bridging.
  • Predicting water displacement and its impact on binding affinity is challenging due to complex site-specific interactions and protein dynamics.
  • Existing methods often fail to account for both protein flexibility and the specific chemical interactions of functional groups.

Purpose of the Study:

  • To develop and validate a method using mixed-solvent molecular dynamics (MixMD) to identify conserved and displaceable water sites on protein surfaces.
  • To assess the ability of MixMD to predict which water molecules are essential for binding and which can be displaced by ligands.
  • To determine if MixMD can predict the types of functional groups capable of displacing specific water molecules.

Main Methods:

  • Utilized mixed-solvent molecular dynamics (MixMD), a cosolvent simulation technique, to model the competition between water and small molecule probes at protein surfaces.
  • Developed an occupancy-based metric to distinguish consistently occupied (conserved) water sites from those prone to displacement.
  • Employed six types of small molecule probes to assess the displaceability of water sites and predict functional group interactions.

Main Results:

  • The MixMD method successfully identified both conserved and displaceable water sites across eight test systems.
  • Conserved water sites were characterized by high occupancy even in the presence of probe molecules.
  • Displaceable water sites showed preferential binding of probe molecules, correlating with known ligand displacement patterns.

Conclusions:

  • MixMD provides a robust approach for identifying critical water sites in protein-ligand binding.
  • The method accurately predicts water site displaceability and the nature of interactions involved in ligand binding.
  • MixMD enhances the understanding of water's role in modulating protein-ligand binding affinity and can guide drug design.