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Protein sequence optimization with a pairwise decomposable penalty for buried unsatisfied hydrogen bonds

In aqueous solution, polar groups make hydrogen bonds with water, and hence burial of such groups in the interior of a protein is unfavorable unless the loss of hydrogen bonds with water is compensated by formation of new ones with other protein groups. For this reason, buried “unsatisfied” polar gr...

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Detalles Bibliográficos
Autores principales: Coventry, Brian, Baker, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971855/
https://www.ncbi.nlm.nih.gov/pubmed/33684097
http://dx.doi.org/10.1371/journal.pcbi.1008061
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author Coventry, Brian
Baker, David
author_facet Coventry, Brian
Baker, David
author_sort Coventry, Brian
collection PubMed
description In aqueous solution, polar groups make hydrogen bonds with water, and hence burial of such groups in the interior of a protein is unfavorable unless the loss of hydrogen bonds with water is compensated by formation of new ones with other protein groups. For this reason, buried “unsatisfied” polar groups making no hydrogen bonds are very rare in proteins. Efficiently representing the energetic cost of unsatisfied hydrogen bonds with a pairwise-decomposable energy term during protein design is challenging since whether or not a group is satisfied depends on all of its neighbors. Here we describe a method for assigning a pairwise-decomposable energy to sidechain rotamers such that following combinatorial sidechain packing, buried unsaturated polar atoms are penalized. The penalty can be any quadratic function of the number of unsatisfied polar groups, and can be computed very rapidly. We show that inclusion of this term in Rosetta sidechain packing calculations substantially reduces the number of buried unsatisfied polar groups.
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spelling pubmed-79718552021-03-31 Protein sequence optimization with a pairwise decomposable penalty for buried unsatisfied hydrogen bonds Coventry, Brian Baker, David PLoS Comput Biol Research Article In aqueous solution, polar groups make hydrogen bonds with water, and hence burial of such groups in the interior of a protein is unfavorable unless the loss of hydrogen bonds with water is compensated by formation of new ones with other protein groups. For this reason, buried “unsatisfied” polar groups making no hydrogen bonds are very rare in proteins. Efficiently representing the energetic cost of unsatisfied hydrogen bonds with a pairwise-decomposable energy term during protein design is challenging since whether or not a group is satisfied depends on all of its neighbors. Here we describe a method for assigning a pairwise-decomposable energy to sidechain rotamers such that following combinatorial sidechain packing, buried unsaturated polar atoms are penalized. The penalty can be any quadratic function of the number of unsatisfied polar groups, and can be computed very rapidly. We show that inclusion of this term in Rosetta sidechain packing calculations substantially reduces the number of buried unsatisfied polar groups. Public Library of Science 2021-03-08 /pmc/articles/PMC7971855/ /pubmed/33684097 http://dx.doi.org/10.1371/journal.pcbi.1008061 Text en © 2021 Coventry, Baker http://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/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Coventry, Brian
Baker, David
Protein sequence optimization with a pairwise decomposable penalty for buried unsatisfied hydrogen bonds
title Protein sequence optimization with a pairwise decomposable penalty for buried unsatisfied hydrogen bonds
title_full Protein sequence optimization with a pairwise decomposable penalty for buried unsatisfied hydrogen bonds
title_fullStr Protein sequence optimization with a pairwise decomposable penalty for buried unsatisfied hydrogen bonds
title_full_unstemmed Protein sequence optimization with a pairwise decomposable penalty for buried unsatisfied hydrogen bonds
title_short Protein sequence optimization with a pairwise decomposable penalty for buried unsatisfied hydrogen bonds
title_sort protein sequence optimization with a pairwise decomposable penalty for buried unsatisfied hydrogen bonds
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971855/
https://www.ncbi.nlm.nih.gov/pubmed/33684097
http://dx.doi.org/10.1371/journal.pcbi.1008061
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