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

Genetic Screens

Genetic Screens

Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which...

In vitro Mutagenesis

In vitro Mutagenesis

In-vitro Mutagenesis

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.

You might also read

Related Articles

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

Sort by

Same author

Biocatalytic cascades enable manufacture of the macrocyclic peptide enlicitide.

Science (New York, N.Y.)·2026

Same author

Profiling of Diverse Pyridoxal-5'-Phosphate Dependent Enzymes Reveals Promiscuous Aldolase Activity with (2-Azaaryl)methanamines.

Journal of the American Chemical Society·2025

Same author

The structure of a NEMO construct engineered for screening reveals novel determinants of inhibition.

Structure (London, England : 1993)·2025

Same author

Combining computational modeling and experimental library screening to affinity-mature VEEV-neutralizing antibody F5.

Protein science : a publication of the Protein Society·2025

Same author

A comparison of antibody-antigen complex sequence-to-structure prediction methods and their systematic biases.

Protein science : a publication of the Protein Society·2024

Same author

A Comparison of Antibody-Antigen Complex Sequence-to-Structure Prediction Methods and their Systematic Biases.

bioRxiv : the preprint server for biology·2024

Same journal

Macromolecular crowding inhibits degradation of alpha-synuclein amyloid fibrils induced by cathepsins and MMP9.

Protein science : a publication of the Protein Society·2026

Same journal

Sequence-encoded differences in the conformational ensembles of CITED transcriptional activation domains impact coactivator binding.

Protein science : a publication of the Protein Society·2026

Same journal

The phospholipid biosynthesis enzyme PlsB contains three distinct domains for membrane association, lysophosphatidic acid synthesis, and dimerization.

Protein science : a publication of the Protein Society·2026

Same journal

Structural basis of ligand selectivity in FAD/NAD(P)H-dependent dehydrogenases: insights from trypanothione reductase and type II NADH dehydrogenase.

Protein science : a publication of the Protein Society·2026

Same journal

Achieving protease substrate-specific inhibition by mAb dual functional selections.

Protein science : a publication of the Protein Society·2026

Same journal

How important are quantum mechanical effects in controlling biological functions: Enzymes, electron transfer and bird navigation.

Protein science : a publication of the Protein Society·2026

See all related articles

Search research articles

Related Experiment Video

Updated: Apr 18, 2026

A Protocol for Functional Assessment of Whole-Protein Saturation Mutagenesis Libraries Utilizing High-Throughput Sequencing

A Protocol for Functional Assessment of Whole-Protein Saturation Mutagenesis Libraries Utilizing High-Throughput Sequencing

Published on: July 3, 2016

Structure-based design of combinatorial mutagenesis libraries.

Deeptak Verma¹, Gevorg Grigoryan, Chris Bailey-Kellogg

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

Protein Science : a Publication of the Protein Society

|January 23, 2015

Summary

This summary is machine-generated.

Computational protein design using Structure-based Optimization of Combinatorial Mutagenesis (SOCoM) optimizes large libraries for improved protein variants. SOCoM enhances discovery of beneficial mutations by focusing on productive sequence space.

Keywords:

cluster expansion combinatorial library high-throughput screening protein design space structure-based protein design

More Related Videos

Mutagenesis and Functional Selection Protocols for Directed Evolution of Proteins in E. coli

Mutagenesis and Functional Selection Protocols for Directed Evolution of Proteins in E. coli

Published on: March 16, 2011

Directed Evolution Method in Saccharomyces cerevisiae: Mutant Library Creation and Screening

Directed Evolution Method in Saccharomyces cerevisiae: Mutant Library Creation and Screening

Published on: April 1, 2016

Related Experiment Videos

Last Updated: Apr 18, 2026

A Protocol for Functional Assessment of Whole-Protein Saturation Mutagenesis Libraries Utilizing High-Throughput Sequencing

A Protocol for Functional Assessment of Whole-Protein Saturation Mutagenesis Libraries Utilizing High-Throughput Sequencing

Published on: July 3, 2016

Mutagenesis and Functional Selection Protocols for Directed Evolution of Proteins in E. coli

Mutagenesis and Functional Selection Protocols for Directed Evolution of Proteins in E. coli

Published on: March 16, 2011

Directed Evolution Method in Saccharomyces cerevisiae: Mutant Library Creation and Screening

Directed Evolution Method in Saccharomyces cerevisiae: Mutant Library Creation and Screening

Published on: April 1, 2016

Area of Science:

Protein Engineering
Computational Biology
Structural Bioinformatics

Background:

High-throughput screening of combinatorial libraries accelerates protein variant development.
Experimental testing is limited to a small fraction of possible protein sequence space.
Computational protein design can focus library design on promising regions of sequence space.

Purpose of the Study:

To present a general-purpose computational method, Structure-based Optimization of Combinatorial Mutagenesis (SOCoM).
To optimize large combinatorial mutagenesis libraries using structural energy calculations.
To enhance the discovery of protein variants with improved properties.

Main Methods:

SOCoM optimizes protein libraries by selecting positions and substitutions based on structural energies.
It employs a combinatorial optimization framework using library-averaged energy potentials.
The method avoids explicit modeling of every possible variant in large libraries.

Main Results:

SOCoM successfully optimized focused libraries for green fluorescent protein, β-lactamase, and lipase A, achieving energies comparable to or better than previous methods.
It also designed larger, more diverse libraries not previously feasible with structure-based methods.
Variants from SOCoM-designed libraries showed substantially better energies than random library approaches.

Conclusions:

SOCoM enables the creation of large-scale combinatorial libraries guided by structural calculations.
This expands the applicability of computational protein design and improves the success rate of discovering beneficial protein variants.
The framework can incorporate various structure-based assessments beyond stability, such as energy gaps between conformational or bound states.