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CoLiDe: Combinatorial Library Design tool for probing protein sequence space

MOTIVATION: Current techniques of protein engineering focus mostly on re-designing small targeted regions or defined structural scaffolds rather than constructing combinatorial libraries of versatile compositions and lengths. This is a missed opportunity because combinatorial libraries are emerging...

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Autores principales: Tretyachenko, Vyacheslav, Voráček, Václav, Souček, Radko, Fujishima, Kosuke, Hlouchová, Klára
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088326/
https://www.ncbi.nlm.nih.gov/pubmed/32956450
http://dx.doi.org/10.1093/bioinformatics/btaa804
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author Tretyachenko, Vyacheslav
Voráček, Václav
Souček, Radko
Fujishima, Kosuke
Hlouchová, Klára
author_facet Tretyachenko, Vyacheslav
Voráček, Václav
Souček, Radko
Fujishima, Kosuke
Hlouchová, Klára
author_sort Tretyachenko, Vyacheslav
collection PubMed
description MOTIVATION: Current techniques of protein engineering focus mostly on re-designing small targeted regions or defined structural scaffolds rather than constructing combinatorial libraries of versatile compositions and lengths. This is a missed opportunity because combinatorial libraries are emerging as a vital source of novel functional proteins and are of interest in diverse research areas. RESULTS: Here, we present a computational tool for Combinatorial Library Design (CoLiDe) offering precise control over protein sequence composition, length and diversity. The algorithm uses evolutionary approach to provide solutions to combinatorial libraries of degenerate DNA templates. We demonstrate its performance and precision using four different input alphabet distribution on different sequence lengths. In addition, a model design and experimental pipeline for protein library expression and purification is presented, providing a proof-of-concept that our protocol can be used to prepare purified protein library samples of up to 10(11)–10(12) unique sequences. CoLiDe presents a composition-centric approach to protein design towards different functional phenomena. AVAILABILITYAND IMPLEMENTATION: CoLiDe is implemented in Python and freely available at https://github.com/voracva1/CoLiDe. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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spelling pubmed-80883262021-05-05 CoLiDe: Combinatorial Library Design tool for probing protein sequence space Tretyachenko, Vyacheslav Voráček, Václav Souček, Radko Fujishima, Kosuke Hlouchová, Klára Bioinformatics Original Papers MOTIVATION: Current techniques of protein engineering focus mostly on re-designing small targeted regions or defined structural scaffolds rather than constructing combinatorial libraries of versatile compositions and lengths. This is a missed opportunity because combinatorial libraries are emerging as a vital source of novel functional proteins and are of interest in diverse research areas. RESULTS: Here, we present a computational tool for Combinatorial Library Design (CoLiDe) offering precise control over protein sequence composition, length and diversity. The algorithm uses evolutionary approach to provide solutions to combinatorial libraries of degenerate DNA templates. We demonstrate its performance and precision using four different input alphabet distribution on different sequence lengths. In addition, a model design and experimental pipeline for protein library expression and purification is presented, providing a proof-of-concept that our protocol can be used to prepare purified protein library samples of up to 10(11)–10(12) unique sequences. CoLiDe presents a composition-centric approach to protein design towards different functional phenomena. AVAILABILITYAND IMPLEMENTATION: CoLiDe is implemented in Python and freely available at https://github.com/voracva1/CoLiDe. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. Oxford University Press 2020-09-21 /pmc/articles/PMC8088326/ /pubmed/32956450 http://dx.doi.org/10.1093/bioinformatics/btaa804 Text en © The Author(s) 2020. Published by Oxford University Press. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Papers
Tretyachenko, Vyacheslav
Voráček, Václav
Souček, Radko
Fujishima, Kosuke
Hlouchová, Klára
CoLiDe: Combinatorial Library Design tool for probing protein sequence space
title CoLiDe: Combinatorial Library Design tool for probing protein sequence space
title_full CoLiDe: Combinatorial Library Design tool for probing protein sequence space
title_fullStr CoLiDe: Combinatorial Library Design tool for probing protein sequence space
title_full_unstemmed CoLiDe: Combinatorial Library Design tool for probing protein sequence space
title_short CoLiDe: Combinatorial Library Design tool for probing protein sequence space
title_sort colide: combinatorial library design tool for probing protein sequence space
topic Original Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088326/
https://www.ncbi.nlm.nih.gov/pubmed/32956450
http://dx.doi.org/10.1093/bioinformatics/btaa804
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