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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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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. |
format | Online Article Text |
id | pubmed-8088326 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
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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