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Entropic Stabilization of Cas4 Protein SSO0001 Predicted with Popcoen
Popcoen is a method for configurational entropy estimation of proteins based on machine-learning. Entropy is predicted with an artificial neural network which was trained on simulation trajectories of a large set of representative proteins. Popcoen is extremely fast compared to other approaches base...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513108/ https://www.ncbi.nlm.nih.gov/pubmed/33265669 http://dx.doi.org/10.3390/e20080580 |
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author | Goethe, Martin Fita, Ignacio Rubi, J. Miguel |
author_facet | Goethe, Martin Fita, Ignacio Rubi, J. Miguel |
author_sort | Goethe, Martin |
collection | PubMed |
description | Popcoen is a method for configurational entropy estimation of proteins based on machine-learning. Entropy is predicted with an artificial neural network which was trained on simulation trajectories of a large set of representative proteins. Popcoen is extremely fast compared to other approaches based on the sampling of a multitude of microstates. Consequently, Popcoen can be incorporated into a large class of protein software which currently neglects configurational entropy for performance reasons. Here, we apply Popcoen to various conformations of the Cas4 protein SSO0001 of Sulfolobus solfataricus, a protein that assembles to a decamer of known toroidal shape. We provide numerical evidence that the native state (NAT) of a SSO0001 monomer has a similar structure to the protomers of the oligomer, where NAT of the monomer is stabilized mainly entropically. Due to its large amount of configurational entropy, NAT has lower free energy than alternative conformations of very low enthalpy and solvation free-energy. Hence, SSO0001 serves as an example case where neglecting configurational entropy leads to incorrect conclusion. Our results imply that no refolding of the subunits is required during oligomerization which suggests that configurational entropy is employed by nature to largely enhance the rate of assembly. |
format | Online Article Text |
id | pubmed-7513108 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75131082020-11-09 Entropic Stabilization of Cas4 Protein SSO0001 Predicted with Popcoen Goethe, Martin Fita, Ignacio Rubi, J. Miguel Entropy (Basel) Article Popcoen is a method for configurational entropy estimation of proteins based on machine-learning. Entropy is predicted with an artificial neural network which was trained on simulation trajectories of a large set of representative proteins. Popcoen is extremely fast compared to other approaches based on the sampling of a multitude of microstates. Consequently, Popcoen can be incorporated into a large class of protein software which currently neglects configurational entropy for performance reasons. Here, we apply Popcoen to various conformations of the Cas4 protein SSO0001 of Sulfolobus solfataricus, a protein that assembles to a decamer of known toroidal shape. We provide numerical evidence that the native state (NAT) of a SSO0001 monomer has a similar structure to the protomers of the oligomer, where NAT of the monomer is stabilized mainly entropically. Due to its large amount of configurational entropy, NAT has lower free energy than alternative conformations of very low enthalpy and solvation free-energy. Hence, SSO0001 serves as an example case where neglecting configurational entropy leads to incorrect conclusion. Our results imply that no refolding of the subunits is required during oligomerization which suggests that configurational entropy is employed by nature to largely enhance the rate of assembly. MDPI 2018-08-07 /pmc/articles/PMC7513108/ /pubmed/33265669 http://dx.doi.org/10.3390/e20080580 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Goethe, Martin Fita, Ignacio Rubi, J. Miguel Entropic Stabilization of Cas4 Protein SSO0001 Predicted with Popcoen |
title | Entropic Stabilization of Cas4 Protein SSO0001 Predicted with Popcoen |
title_full | Entropic Stabilization of Cas4 Protein SSO0001 Predicted with Popcoen |
title_fullStr | Entropic Stabilization of Cas4 Protein SSO0001 Predicted with Popcoen |
title_full_unstemmed | Entropic Stabilization of Cas4 Protein SSO0001 Predicted with Popcoen |
title_short | Entropic Stabilization of Cas4 Protein SSO0001 Predicted with Popcoen |
title_sort | entropic stabilization of cas4 protein sso0001 predicted with popcoen |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513108/ https://www.ncbi.nlm.nih.gov/pubmed/33265669 http://dx.doi.org/10.3390/e20080580 |
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