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

Conserved Binding Sites01:49

Conserved Binding Sites

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 analyses the...
Protein Folding01:25

Protein Folding

Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Folding01:22

Protein Folding

Overview
Mutations01:35

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Mutations01:39

Mutations

Overview
Protein Denaturation01:28

Protein Denaturation

The function of proteins depends on their native three-dimensional structure, which is dictated by the amino acid sequence of the specific protein. Folding of the polypeptide chain takes place under specific conditions that energetically favor the folded conformation. In contrast, protein denaturation occurs spontaneously under unfavorable conditions that disrupt the integrity of the folded conformation. Thus, the chemical and physical environment of a protein, such as significant changes in pH...

You might also read

Related Articles

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

Sort by
Same author

Computational design of orthogonal TCR α/β interfaces for dual-TCR therapeutics.

bioRxiv : the preprint server for biology·2026
Same author

Stabilizing proteins, simplified: A Rosetta-based webtool for predicting favorable mutations.

Protein science : a publication of the Protein Society·2022
Same author

Correction to "The Rosetta All-Atom Energy Function for Macromolecular Modeling and Design".

Journal of chemical theory and computation·2022
Same author

PyRosetta Jupyter Notebooks Teach Biomolecular Structure Prediction and Design.

Biophysicist (Rockville, Md.)·2022
Same author

Comparative Analysis of Sulfonium-π, Ammonium-π, and Sulfur-π Interactions and Relevance to SAM-Dependent Methyltransferases.

Journal of the American Chemical Society·2022
Same author

Ensuring scientific reproducibility in bio-macromolecular modeling via extensive, automated benchmarks.

Nature communications·2021

Related Experiment Video

Updated: Jun 4, 2026

Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches
05:56

Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches

Published on: October 13, 2022

Role of conformational sampling in computing mutation-induced changes in protein structure and stability.

Elizabeth H Kellogg1, Andrew Leaver-Fay, David Baker

  • 1Department of Biochemistry, University of Washington, Seattle, WA 98105, USA.

Proteins
|February 3, 2011
PubMed
Summary

Predicting protein stability changes from amino acid substitutions is crucial. Similar prediction accuracy is achieved with varying conformational sampling, provided force field resolution matches sampling methods.

More Related Videos

Structure-Based Simulation and Sampling of Transcription Factor Protein Movements along DNA from Atomic-Scale Stepping to Coarse-Grained Diffusion
09:17

Structure-Based Simulation and Sampling of Transcription Factor Protein Movements along DNA from Atomic-Scale Stepping to Coarse-Grained Diffusion

Published on: March 1, 2022

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

Related Experiment Videos

Last Updated: Jun 4, 2026

Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches
05:56

Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches

Published on: October 13, 2022

Structure-Based Simulation and Sampling of Transcription Factor Protein Movements along DNA from Atomic-Scale Stepping to Coarse-Grained Diffusion
09:17

Structure-Based Simulation and Sampling of Transcription Factor Protein Movements along DNA from Atomic-Scale Stepping to Coarse-Grained Diffusion

Published on: March 1, 2022

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

Area of Science:

  • Computational biology
  • Protein structure and stability analysis
  • Bioinformatics

Background:

  • Single amino acid substitutions can alter protein stability and structure.
  • High-throughput sequencing increases the rate of discovering sequence polymorphisms.
  • Accurate prediction methods are needed to understand mutation effects.

Purpose of the Study:

  • To explore the performance of computational protocols for predicting protein stability and structural changes due to mutations.
  • To investigate the impact of varying conformational sampling on prediction accuracy.
  • To identify areas for improvement in current modeling methodologies.

Main Methods:

  • Utilized computational protocols with diverse conformational sampling.
  • Matched the resolution of the force field to the resolution of the sampling method.
  • Analyzed structural changes and changes in folding-free energy.

Main Results:

  • Protocols with different conformational sampling levels achieved similar prediction performances for stability changes.
  • Force field resolution must be matched to the sampling method's resolution for accurate predictions.
  • Backbone sampling methods can accurately predict structural changes but may negatively impact predictions when changes are negligible.

Conclusions:

  • Protein stability prediction accuracy is less dependent on the extent of conformational sampling than previously thought.
  • Matching force field and sampling resolution is key for reliable computational predictions.
  • Further improvements are needed in modeling desolvation, buried polar interactions, and unfolded states.