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

Computational stabilization of human growth hormone.

Anton V Filikov1, Robert J Hayes, Peizhi Luo

  • 1Xencor, Inc., Monrovia, California 91016, USA.

Protein Science : a Publication of the Protein Society
|May 22, 2002
PubMed
Summary

Computational redesign improved the stability of human growth hormone (hGH). This protein engineering advance offers potential for more convenient drug delivery and enhanced therapeutic efficacy.

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

Blastoid Mantle Cell Lymphoma in the Leukemic Phase: Resolving a Morphological Dilemma Through Flow Cytometry.

Cureus·2026
Same author

Integrative analysis of nanopore direct RNA sequencing data reveals a global impact of pseudouridylation on m<sup>6</sup>A and m<sup>5</sup>C modifications.

NPJ precision oncology·2026
Same author

Mechanical and structural analysis of graphene-PMMA laminate.

Nature communications·2025
Same author

Emerging molecular targets and natural therapeutics for idiopathic pulmonary fibrosis: Insights into mechanisms, risks, and COVID-19 links.

Respiratory medicine·2025
Same author

HDAC7 promotes renal cancer progression by reprogramming branched-chain amino acid metabolism.

Science advances·2025
Same author

LncRNAs in oncogenic microenvironment: from threat to therapy.

Frontiers in cell and developmental biology·2025

Area of Science:

  • Biochemistry
  • Protein Engineering
  • Computational Biology

Background:

  • Recombinant human growth hormone (hGH) is crucial for treating growth deficiencies but suffers from poor stability and bioavailability.
  • Current administration requires frequent injections, impacting patient compliance and treatment efficacy.
  • Developing more stable hGH formulations or alternative delivery methods is a key therapeutic goal.

Purpose of the Study:

  • To computationally redesign human growth hormone (hGH) for enhanced thermostability.
  • To explore the potential of improved hGH stability for advanced drug delivery systems.
  • To validate a computational protein design algorithm for therapeutic protein optimization.

Main Methods:

  • Utilized a combinatorial optimization algorithm based on the dead-end elimination theorem for protein redesign.

Related Experiment Videos

  • Employed an empirical free energy function, augmented with entropic terms, for scoring designed protein sequences.
  • Optimized scoring function parameters by minimizing mutations relative to wild-type hGH.
  • Selected 45 core residues for targeted optimization.
  • Main Results:

    • Designed hGH variants exhibited 6-10 mutations and increased melting temperatures by up to 16°C.
    • The engineered proteins retained biological activity in cell proliferation assays.
    • Demonstrated the effectiveness of the developed free energy function in automated protein design.

    Conclusions:

    • Computational redesign successfully enhanced the thermostability of human growth hormone (hGH).
    • The engineered, more stable hGH variants hold promise for improved pharmacokinetics and shelf-life.
    • This study validates the utility of the computational approach for designing more robust therapeutic proteins.