Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Mismatch Repair

Mismatch Repair

Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...

Mismatch Repair

Mismatch Repair

Mutations

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...

Mutations

Mutations

Mutations

Mutations

Conservative Site-specific Recombination and Phase Variation

Conservative Site-specific Recombination and Phase Variation

Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...

You might also read

Related Articles

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

Sort by

Same author

A structure-based tool to interpret the significance of kinase mutations in clinical next generation sequencing in cancer.

Frontiers in oncology·2025

Same author

A role for pH dynamics regulating transcription factor DNA-binding selectivity.

Nucleic acids research·2025

Same author

Identifying FUS amyotrophic lateral sclerosis disease signatures in patient dermal fibroblasts.

Developmental cell·2024

Same author

A role for pH dynamics regulating transcription factor DNA binding selectivity.

bioRxiv : the preprint server for biology·2024

Same author

BCR::ABL1 kinase N-lobe mutants confer moderate to high degrees of resistance to asciminib.

Blood·2024

Same author

Clustering Protein Binding Pockets and Identifying Potential Drug Interactions: A Novel Ligand-Based Featurization Method.

Journal of chemical information and modeling·2023

Same journal

BioMatics 1.0: A Wasserstein Distance Approach for Next-Generation Multiple Sequence Alignment.

Proteins·2026

Same journal

Engineered HSP90-MP65 Bivalent Fusion Antigen: A Novel Vaccine Candidate Against Invasive Candidiasis.

Proteins·2026

Same journal

Physics-Based Energy Functions for Computational Protein Design.

Proteins·2026

Same journal

Impact of Stabilizing Osmolytes on the Conformational Dynamics of Human and Rat Islet Amyloid Polypeptides.

Proteins·2026

Same journal

Stabilization of Bone Morphogenetic Protein-2 at Physiological pH: Contrasting Roles of CHAPS and Arginine in Aggregation Inhibition.

Proteins·2026

Same journal

Structural Insights Into the Function of Leishmania major Adenylosuccinate Lyase.

Proteins·2026

See all related articles

Search research articles

Related Experiment Video

Updated: Jun 4, 2026

Assessing Somatic Hypermutation in Ramos B Cells after Overexpression or Knockdown of Specific Genes

Assessing Somatic Hypermutation in Ramos B Cells after Overexpression or Knockdown of Specific Genes

Published on: November 1, 2011

Effects of somatic mutations on CDR loop flexibility during affinity maturation.

Sergio E Wong¹, Ben D Sellers, Matthew P Jacobson

¹Graduate Group in Biophysics, Department of Pharmaceutical Chemistry, University of California, San Francisco, California, USA. wong105@llnl.gov

|February 3, 2011

Summary

This summary is machine-generated.

Somatic mutations during antibody affinity maturation rigidify complementarity-determining regions (CDRs), reducing the entropic cost of binding. Molecular dynamics simulations revealed how these mutations restrict CDR motility and identified new mutations that could decrease antibody binding by increasing flexibility.

More Related Videos

Studying Age-dependent Genomic Instability using the S. cerevisiae Chronological Lifespan Model

Studying Age-dependent Genomic Instability using the S. cerevisiae Chronological Lifespan Model

Published on: September 29, 2011

CRISPR-Mediated Reorganization of Chromatin Loop Structure

CRISPR-Mediated Reorganization of Chromatin Loop Structure

Published on: September 14, 2018

Related Experiment Videos

Last Updated: Jun 4, 2026

Assessing Somatic Hypermutation in Ramos B Cells after Overexpression or Knockdown of Specific Genes

Assessing Somatic Hypermutation in Ramos B Cells after Overexpression or Knockdown of Specific Genes

Published on: November 1, 2011

Studying Age-dependent Genomic Instability using the S. cerevisiae Chronological Lifespan Model

Studying Age-dependent Genomic Instability using the S. cerevisiae Chronological Lifespan Model

Published on: September 29, 2011

CRISPR-Mediated Reorganization of Chromatin Loop Structure

CRISPR-Mediated Reorganization of Chromatin Loop Structure

Published on: September 14, 2018

Area of Science:

Immunology
Structural Biology
Computational Biology

Background:

Antibody affinity maturation enhances binding to antigens.
Somatic mutations are key to this process, potentially by prearranging CDRs.
The precise impact of mutations on CDR flexibility remains poorly understood.

Purpose of the Study:

To investigate how somatic mutations influence CDR flexibility during antibody maturation.
To analyze the conformational dynamics of CDRs in mature antibodies versus their germline precursors.
To predict mutations affecting antibody binding through altered CDR flexibility.

Main Methods:

Molecular dynamics simulations were employed.
Simulations compared four mature antibodies (7G12, AZ28, 28B4, 48G7) with their germline counterparts.
Analysis focused on CDR motility and conformational equilibria.

Main Results:

Mutations acquired during affinity maturation were shown to restrict CDR motility.
The study captured the dynamic equilibrium of the H3 loop in unligigated 7G12.
Simulations predicted novel mutations that are expected to reduce binding affinity by increasing CDR flexibility.

Conclusions:

Antibody affinity maturation involves mutations that decrease CDR flexibility, thereby reducing the entropic penalty of antigen binding.
Understanding CDR dynamics provides insights into antibody engineering and drug design.
Computational simulations offer a powerful tool for predicting the effects of mutations on antibody function.