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 Experiment Videos

PoPMuSiC, an algorithm for predicting protein mutant stability changes: application to prion proteins.

D Gilis1, M Rooman

  • 1Ingénierie Biomoléculaire, Université Libre de Bruxelles, CP 165/64, 50 avenue Roosevelt, 1050 Brussels, Belgium.

Protein Engineering
|March 10, 2001
PubMed
Summary

A new computational tool predicts protein mutations to enhance stability. It identified specific mutations in prion proteins, offering potential therapeutic targets for prion diseases.

Related Concept Videos

You might also read

Related Articles

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

Sort by
Same author

The minor house dust mite allergen Der p 13 is a fatty acid-binding protein and an activator of a TLR2-mediated innate immune response.

Allergy·2016
Same author

A robust method for the joint estimation of yield coefficients and kinetic parameters in bioprocess models.

Biotechnology progress·2009
Same author

A new generation of statistical potentials for proteins.

Biophysical journal·2006
Same author

Protein decoy sets for evaluating energy functions.

Journal of biomolecular structure & dynamics·2004
Same author

PoPMuSiC, rationally designing point mutations in protein structures.

Bioinformatics (Oxford, England)·2002
Same author

Optimality of the genetic code with respect to protein stability and amino-acid frequencies.

Genome biology·2001

Area of Science:

  • Biochemistry
  • Computational Biology
  • Structural Biology

Background:

  • Prion diseases are linked to misfolding of prion proteins.
  • Stabilizing the cellular form of prion proteins may prevent disease progression.
  • Computer-aided design offers a method for targeted protein engineering.

Purpose of the Study:

  • To develop and apply a novel computational tool for designing single-site mutations in proteins.
  • To identify mutations that stabilize the cellular form of prion proteins.
  • To explore mutations that modify protein aggregation propensity.

Main Methods:

  • In silico prediction of all possible point mutations in protein sequences.
  • Estimation of stability changes using linear combinations of database-derived potentials.

Related Experiment Videos

  • Analysis of mutation effects based on solvent accessibility and structural location.

    • Main Results:

    • The tool identified stabilizing mutations in mouse, hamster, and human prion proteins, primarily in the second helix.
    • Key stabilizing mutations include T183-->F, T192-->A, and Q186-->A.
    • A mutation E146-->L was identified to improve helix hydrophobicity without compromising stability, potentially reducing aggregation.

    Conclusions:

    • The developed computational tool effectively predicts stabilizing and functionally relevant mutations in prion proteins.
    • Identified mutations, particularly T183-->F, show significant stabilization potential but require careful consideration due to potential effects on glycosylation.
    • Selected mutations provide promising candidates for experimental validation in the context of prion disease research.