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Related Concept Videos

In vitro Mutagenesis01:16

In vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
In-vitro Mutagenesis01:16

In-vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
Mismatch Repair01:20

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...
Combinatorial Gene Control02:33

Combinatorial Gene Control

Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
Mutagenicity and Carcinogenicity01:25

Mutagenicity and Carcinogenicity

Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
Spontaneous and Induced Mutations01:30

Spontaneous and Induced Mutations

Spontaneous mutations arise infrequently during DNA replication due to errors in the process. A key factor behind these errors is tautomeric shifts in nitrogenous bases, where bases transition from keto to enol forms or amino to imino forms. This shift can alter base-pairing rules, leading to mutations. Additionally, reactive oxygen species (ROS) arising from aerobic metabolism can damage DNA, resulting in depurination (loss of a purine base) or depyrimidination (loss of a pyrimidine base).

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Related Experiment Video

Updated: May 29, 2026

Optogenetic Random Mutagenesis Using Histone-miniSOG in C. elegans
04:51

Optogenetic Random Mutagenesis Using Histone-miniSOG in C. elegans

Published on: November 14, 2016

Optimization of combinatorial mutagenesis.

Andrew S Parker1, Karl E Griswold, Chris Bailey-Kellogg

  • 1Department of Computer Science, Dartmouth College, Hanover, New Hampshire, USA.

Journal of Computational Biology : a Journal of Computational Molecular Cell Biology
|September 20, 2011
PubMed
Summary
This summary is machine-generated.

We developed Optimization of Combinatorial Mutagenesis (OCoM) to design better protein variant libraries. OCoM efficiently identifies optimal mutations, improving the discovery of beneficial protein variants with enhanced properties.

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Site-Directed Mutagenesis for In Vitro and In Vivo Experiments Exemplified with RNA Interactions in Escherichia Coli
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Site-Directed Mutagenesis for In Vitro and In Vivo Experiments Exemplified with RNA Interactions in Escherichia Coli

Published on: February 5, 2019

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Last Updated: May 29, 2026

Optogenetic Random Mutagenesis Using Histone-miniSOG in C. elegans
04:51

Optogenetic Random Mutagenesis Using Histone-miniSOG in C. elegans

Published on: November 14, 2016

Site-Directed Mutagenesis for In Vitro and In Vivo Experiments Exemplified with RNA Interactions in Escherichia Coli
07:04

Site-Directed Mutagenesis for In Vitro and In Vivo Experiments Exemplified with RNA Interactions in Escherichia Coli

Published on: February 5, 2019

Area of Science:

  • Protein engineering
  • Computational biology
  • Biotechnology

Background:

  • Combinatorial site-directed mutagenesis is used to engineer proteins with improved properties.
  • Current methods often have a low hit-rate for beneficial variants.
  • There is a need for methods to optimize the selection of mutations for library construction.

Purpose of the Study:

  • To develop a computational approach for optimizing the design of combinatorial mutagenesis libraries.
  • To improve the efficiency and success rate of identifying beneficial protein variants.
  • To balance library quality (e.g., stability, activity) with sequence novelty.

Main Methods:

  • Developed Optimization of Combinatorial Mutagenesis (OCoM) for selecting optimal mutation positions and sets.
  • OCoM utilizes one- and two-body sequence potentials to evaluate library quality and novelty.
  • Employs dynamic programming for the one-body case and integer programming for the two-body case.

Main Results:

  • OCoM efficiently optimizes combinatorial libraries, even for large proteins and millions of variants.
  • Demonstrated effectiveness on green fluorescent protein, cytochrome P450, and beta lactamase.
  • Successfully designed libraries by balancing variant quality and novelty.

Conclusions:

  • OCoM provides an efficient and effective method for designing protein variant libraries.
  • Enables exploration of trade-offs between library quality, novelty, and construction methods.
  • Facilitates the identification of optimal libraries for experimental evaluation.