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

Protein Folding01:25

Protein Folding

8.8K
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...
8.8K
Protein Folding01:22

Protein Folding

112.3K
Overview
112.3K
Protein Folding01:22

Protein Folding

29.7K
29.7K
Molecular Chaperones and Protein Folding03:00

Molecular Chaperones and Protein Folding

14.7K
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
14.7K
Bacterial Protein Maturation01:26

Bacterial Protein Maturation

744
Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
744
Conservation of Protein Domains Over Different Proteins02:26

Conservation of Protein Domains Over Different Proteins

11.8K
Protein domains are small structurally independent units that are part of a single amino acid chain.  Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
11.8K

You might also read

Related Articles

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

Sort by
Same author

<i>In vivo</i> assembly to switch fluorescent protein expression in <i>Escherichia coli</i>: a simple laboratory class to introduce molecular cloning.

Journal of microbiology & biology education·2026
Same author

An Automated Workflow Leveraging Machine Learning for Physical Titer Determination from Cryo-TEM Images of Adeno-Associated Virus Capsids.

Chemical & biomedical imaging·2026
Same author

Inflammatory blood-based biomarkers to aid in the assessment and prognostication of traumatic brain injury: a TRACK-TBI study.

Journal of neuroinflammation·2026
Same author

The association between concussion and autonomic nervous system responses to a cognitive stressor.

The Clinical neuropsychologist·2026
Same author

A closed-head, rotational traumatic brain injury model demonstrates deficits in righting reflex, neurological function, and auditory brainstem responses in rats.

Brain injury·2026
Same author

Deconvoluting Biophysical Factors that Influence Long-Term Aggregation Rates of High-Concentration Monoclonal Antibody Formulations.

Molecular pharmaceutics·2025

Related Experiment Video

Updated: May 1, 2026

4D Imaging of Protein Aggregation in Live Cells
08:59

4D Imaging of Protein Aggregation in Live Cells

Published on: April 5, 2013

18.3K

Conformational stability as a design target to control protein aggregation.

Joseph A Costanzo1, Christopher J O'Brien, Kathryn Tiller

  • 1Department of Chemical Engineering, University of Virginia, Charlottesville, VA 22903, USA.

Protein Engineering, Design & Selection : PEDS
|April 12, 2014
PubMed
Summary

Computational protein design can mitigate non-native protein aggregation by increasing conformational stability. This study used RosettaDesign to engineer human γD crystallin, showing stability improvements correlate with reduced aggregation rates.

Keywords:
computational protein designprotein aggregationprotein engineeringprotein folding

More Related Videos

Evaluation of the Impact of Protein Aggregation on Cellular Oxidative Stress in Yeast
11:04

Evaluation of the Impact of Protein Aggregation on Cellular Oxidative Stress in Yeast

Published on: June 23, 2018

7.0K
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

9.6K

Related Experiment Videos

Last Updated: May 1, 2026

4D Imaging of Protein Aggregation in Live Cells
08:59

4D Imaging of Protein Aggregation in Live Cells

Published on: April 5, 2013

18.3K
Evaluation of the Impact of Protein Aggregation on Cellular Oxidative Stress in Yeast
11:04

Evaluation of the Impact of Protein Aggregation on Cellular Oxidative Stress in Yeast

Published on: June 23, 2018

7.0K
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

9.6K

Area of Science:

  • Biochemistry
  • Biotechnology
  • Protein Engineering

Background:

  • Non-native protein aggregation is a significant challenge in biotechnology, impacting product efficacy and potentially causing disease.
  • Aggregation can compromise biological activity or trigger immune responses.
  • Amyloid fibril formation, linked to diseases, arises from specific aggregation pathways.

Purpose of the Study:

  • To investigate computational strategies for mitigating protein aggregation by enhancing conformational stability.
  • To use human γD crystallin (γD-crys) as a model to test if increasing the free energy for unfolding (ΔGunf) reduces aggregation rates.
  • To explore stabilizing domain-domain interfaces and less stable domains as mutational approaches.

Main Methods:

  • Utilized RosettaDesign, a computational protein design algorithm, to identify point mutations.
  • Applied two mutational strategies: stabilizing the less stable domain and the domain-domain interface.
  • Experimentally assessed the impact of mutations on aggregation rates and conformational stability (ΔGunf).

Main Results:

  • While predicted free energies showed weak correlation with experimental ΔGunf, aggregation rates correlated well with changes in ΔGunf.
  • Decreased aggregation rates were observed with increased experimental ΔGunf, supporting conformational stability as a design target.
  • Identified that conformational stability is not the sole determinant of aggregation rates in natively folded proteins.

Conclusions:

  • Computational design can enhance protein conformational stability to mitigate non-native aggregation.
  • Targeting conformational stability is a viable strategy, though not the only factor, for controlling protein aggregation.
  • Further research is needed to fully understand and control protein aggregation mechanisms in biotechnological applications.