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

Modulating calmodulin binding specificity through computational protein design.

Julia M Shifman1, Stephen L Mayo

  • 1Howard Hughes Medical Institute and Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.

Journal of Molecular Biology
|October 17, 2002
PubMed
Summary
This summary is machine-generated.

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

Hydrogel Encapsulation of a Designed Fluorescent Protein Biosensor for Continuous Measurements of Sub-100 nM Nicotine.

ACS applied bio materials·2025
Same author

Recruiting ESCRT to single-chain heterotrimer peptide MHCI releases antigen-presenting vesicles that stimulate T cells selectively.

Proceedings of the National Academy of Sciences of the United States of America·2025
Same author

Engineered N-TIMP2 Variant Specifically Targeting MMP-9 Exhibits Potent Anti-Glioblastoma Activity.

Biomolecules·2025
Same author

Engineered protein inhibitors for precise targeting of matrix metalloproteinases.

Trends in biochemical sciences·2025
Same author

ProBASS-a language model with sequence and structural features for predicting the effect of mutations on binding affinity.

Bioinformatics (Oxford, England)·2025
Same author

CDRxAbs: antibody small-molecule conjugates with computationally designed target-binding synergy.

Protein engineering, design & selection : PEDS·2025
Same journal

Biologically Relevant, Cationic Residues in Human Rhinovirus Stabilize Capsid-Bound RNA Duplexes, and Restrict Capsid Flexibility.

Journal of molecular biology·2026
Same journal

Cryo-EM structures of phage T4 infection intermediate.

Journal of molecular biology·2026
Same journal

A classic fold with a twist: Structural architecture of Dhillonvirus phage Bas18.

Journal of molecular biology·2026
Same journal

Tesorai Search: cloud-based database search engine boosts identifications for mass spectrometry proteomics with a pretrained peptide-spectrum deep-learning model.

Journal of molecular biology·2026
Same journal

Characterization of diverse functions of NRF1 nuclear localization sequence.

Journal of molecular biology·2026
Same journal

UPF3A and UPF3B shape the transcriptome cooperatively yet oppose cell function.

Journal of molecular biology·2026
See all related articles

Computational redesign enhanced calmodulin (CaM) binding specificity for smooth muscle myosin light chain kinase (smMLCK). The engineered CaM_8 protein showed improved affinity for smMLCK while reducing binding to other targets.

Area of Science:

  • Biochemistry
  • Computational Biology
  • Protein Engineering

Background:

  • Calmodulin (CaM) is a versatile Ca(2+)-binding protein regulating diverse targets.
  • Optimizing CaM's binding interface is crucial for understanding and engineering protein specificity.

Purpose of the Study:

  • To computationally redesign the CaM binding interface for enhanced specificity towards smooth muscle myosin light chain kinase (smMLCK).
  • To investigate the effectiveness of the ORBIT program in achieving targeted protein-ligand binding specificity.

Main Methods:

  • Utilized the Optimization of Rotamers by Iterative Techniques (ORBIT) program for protein redesign.
  • Employed a physics-based force field and the Dead-End Elimination theorem to explore vast sequence space (10^22 possibilities).

Related Experiment Videos

  • Constructed and characterized an eight-residue mutant of CaM (CaM_8) and tested its binding affinity to multiple target peptides.

    • Main Results:

    • The engineered CaM_8 mutant exhibited high binding affinity to the smMLCK peptide (1.3 nM), comparable to wild-type CaM (1.8 nM).
    • CaM_8 demonstrated significantly reduced binding affinity (1.5-fold to 86-fold) to six other CaM target peptides.
    • The results confirm increased binding specificity of CaM_8 for smMLCK over other targets.

    Conclusions:

    • Computational redesign using ORBIT successfully enhanced CaM's binding specificity for smMLCK.
    • This approach provides a valuable framework for designing novel protein receptors with tailored binding properties.
    • Further studies can elucidate the fundamental principles governing binding specificity in protein-ligand interactions.