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

Asparagine deamidation: pH-dependent mechanism from density functional theory.

Baron Peters1, Bernhardt L Trout

  • 1Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.

Biochemistry
|April 19, 2006
PubMed
Summary

Asparagine deamidation, crucial in cancer therapy and antibody stability, was computationally studied. Understanding its pH-dependent reaction pathways can improve drug efficacy and protein formulations.

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

Understanding Size Distributions during Lipid Nanoparticle Manufacturing through Mechanistic Modeling.

ACS omega·2026
Same author

Improving individual committor estimates and data efficiency in reaction coordinate tests with the empirical Bayes method.

The Journal of chemical physics·2026
Same author

Modular Design of Vacuum Systems for Lyophilization.

Industrial & engineering chemistry research·2026
Same author

Continuous lyophilization of suspended vials with per-vial inline analytics.

Journal of pharmaceutical sciences·2026
Same author

End-to-end digital twin software for continuous mRNA manufacturing.

International journal of pharmaceutics·2025
Same author

Mechanistic modeling of lipid nanoparticle formation for the delivery of nucleic acid therapeutics.

Biotechnology advances·2025

Area of Science:

  • Biochemistry
  • Computational Chemistry
  • Protein Chemistry

Background:

  • Asparagine deamidation is critical in chemotherapy-induced apoptosis.
  • It poses a significant challenge in the formulation of monoclonal antibodies.
  • The elementary reactions underlying asparagine deamidation remain poorly understood.

Purpose of the Study:

  • To elucidate the fundamental reaction mechanisms of asparagine deamidation.
  • To investigate the pH-dependent kinetics of asparagine deamidation.
  • To provide insights for improving protein formulations and understanding therapeutic outcomes.

Main Methods:

  • Utilized B3LYP/6-31+G(d,p)/COSMO-RS calculations to identify stable structures and transition states.
  • Developed a kinetic model incorporating calculated rate constants to analyze pH dependence.

Related Experiment Videos

  • Compared the computational kinetic model with a pseudo-steady-state model.

    • Main Results:

    • At low pH, direct acid-catalyzed hydrolysis to aspartate was identified as the primary deamidation pathway.
    • At neutral to basic pH, deamidation proceeds via a tetrahedral intermediate.
    • Two distinct pathways and three rate-determining steps for intermediate conversion were revealed, varying with pH.

    Conclusions:

    • The computational model qualitatively replicates the experimentally observed pH-dependent rate constant for asparagine deamidation.
    • Identified rate-determining transition state structures offer mechanistic understanding.
    • Findings can aid in optimizing protein formulations and understanding chemotherapy-induced apoptosis.