In silico investigation and surmounting of lipopolysaccharide barrier in Gram-negative bacteria: how far has molecular dynamics come?

Lipopolysaccharide (LPS), a main component of the outer membrane of Gram-negative bacteria, has crucial implications on both antibiotic resistance and the overstimulation of the host innate immune system. Fighting against these global concerns calls for the molecular understanding of the barrier fun...

Descripción completa

Detalles Bibliográficos
Autores: González Fernández, Cristina, Bringas Elizalde, Eugenio|||0000-0001-8197-6547, Oostenbrink, Cris, Ortiz Uribe, Inmaculada|||0000-0002-3257-4821
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universidad de Cantabria (UC)
Repositorio:UCrea Repositorio Abierto de la Universidad de Cantabria
Idioma:inglés
OAI Identifier:oai:repositorio.unican.es:10902/26996
Acceso en línea:https://hdl.handle.net/10902/26996
Access Level:acceso abierto
Palabra clave:Lipopolysaccharide (LPS)
Antibiotic resistance
Molecular dynamics (MD)
Enhanced sampling
Free energy calculation
Special-purpose MD supercomputers
id ES_4e65b7f6d61e6ee19d57a3bfa4f09061
oai_identifier_str oai:repositorio.unican.es:10902/26996
network_acronym_str ES
network_name_str España
repository_id_str
spelling In silico investigation and surmounting of lipopolysaccharide barrier in Gram-negative bacteria: how far has molecular dynamics come?González Fernández, CristinaBringas Elizalde, Eugenio|||0000-0001-8197-6547Oostenbrink, CrisOrtiz Uribe, Inmaculada|||0000-0002-3257-4821Lipopolysaccharide (LPS)Antibiotic resistanceMolecular dynamics (MD)Enhanced samplingFree energy calculationSpecial-purpose MD supercomputersLipopolysaccharide (LPS), a main component of the outer membrane of Gram-negative bacteria, has crucial implications on both antibiotic resistance and the overstimulation of the host innate immune system. Fighting against these global concerns calls for the molecular understanding of the barrier function and immunostimulatory ability of LPS. Molecular dynamics (MD) simulations have become an invaluable tool for uncovering important findings in LPS research. While the reach of MD simulations for investigating the immunostimulatory ability of LPS has been already outlined, little attention has been paid to the role of MD simulations for exploring its barrier function and synthesis. Herein, we give an overview about the impact of MD simulations on gaining insight into the shield role and synthesis pathway of LPS, which have attracted considerable attention to discover molecules able to surmount antibiotic resistance, either circumventing LPS defenses or disrupting its synthesis. We specifically focus on the enhanced sampling and free energy calculation methods that have been combined with MD simulations to address such research. We also highlight the use of special-purpose MD supercomputers, the importance of appropriate LPS and ions parameterization to obtain reliable results, and the complementary views that MD and wet-lab experiments provide. Thereby, this work, which covers the last five years of research, apart from outlining the phenomena and strategies that are being explored, evidences the valuable insights that are gained by MD, which may be useful to advance antibiotic design, and what the prospects of this in silico method could be in LPS research.Financial support from the Spanish Ministry of Science, Innovation and Universities under the project RTI2018-093310-B-I00 is gratefully acknowledged.ElsevierUniversidad de Cantabria20222022-01-01journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articlehttps://hdl.handle.net/10902/26996Computational and Structural Biotechnology Journal, 2022, 20, 5886-5901reponame:UCrea Repositorio Abierto de la Universidad de Cantabriainstname:Universidad de Cantabria (UC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repositorio.unican.es:10902/269962026-06-02T12:39:31Z
dc.title.none.fl_str_mv In silico investigation and surmounting of lipopolysaccharide barrier in Gram-negative bacteria: how far has molecular dynamics come?
title In silico investigation and surmounting of lipopolysaccharide barrier in Gram-negative bacteria: how far has molecular dynamics come?
spellingShingle In silico investigation and surmounting of lipopolysaccharide barrier in Gram-negative bacteria: how far has molecular dynamics come?
González Fernández, Cristina
Lipopolysaccharide (LPS)
Antibiotic resistance
Molecular dynamics (MD)
Enhanced sampling
Free energy calculation
Special-purpose MD supercomputers
title_short In silico investigation and surmounting of lipopolysaccharide barrier in Gram-negative bacteria: how far has molecular dynamics come?
title_full In silico investigation and surmounting of lipopolysaccharide barrier in Gram-negative bacteria: how far has molecular dynamics come?
title_fullStr In silico investigation and surmounting of lipopolysaccharide barrier in Gram-negative bacteria: how far has molecular dynamics come?
title_full_unstemmed In silico investigation and surmounting of lipopolysaccharide barrier in Gram-negative bacteria: how far has molecular dynamics come?
title_sort In silico investigation and surmounting of lipopolysaccharide barrier in Gram-negative bacteria: how far has molecular dynamics come?
dc.creator.none.fl_str_mv González Fernández, Cristina
Bringas Elizalde, Eugenio|||0000-0001-8197-6547
Oostenbrink, Cris
Ortiz Uribe, Inmaculada|||0000-0002-3257-4821
author González Fernández, Cristina
author_facet González Fernández, Cristina
Bringas Elizalde, Eugenio|||0000-0001-8197-6547
Oostenbrink, Cris
Ortiz Uribe, Inmaculada|||0000-0002-3257-4821
author_role author
author2 Bringas Elizalde, Eugenio|||0000-0001-8197-6547
Oostenbrink, Cris
Ortiz Uribe, Inmaculada|||0000-0002-3257-4821
author2_role author
author
author
dc.contributor.none.fl_str_mv Universidad de Cantabria
dc.subject.none.fl_str_mv Lipopolysaccharide (LPS)
Antibiotic resistance
Molecular dynamics (MD)
Enhanced sampling
Free energy calculation
Special-purpose MD supercomputers
topic Lipopolysaccharide (LPS)
Antibiotic resistance
Molecular dynamics (MD)
Enhanced sampling
Free energy calculation
Special-purpose MD supercomputers
description Lipopolysaccharide (LPS), a main component of the outer membrane of Gram-negative bacteria, has crucial implications on both antibiotic resistance and the overstimulation of the host innate immune system. Fighting against these global concerns calls for the molecular understanding of the barrier function and immunostimulatory ability of LPS. Molecular dynamics (MD) simulations have become an invaluable tool for uncovering important findings in LPS research. While the reach of MD simulations for investigating the immunostimulatory ability of LPS has been already outlined, little attention has been paid to the role of MD simulations for exploring its barrier function and synthesis. Herein, we give an overview about the impact of MD simulations on gaining insight into the shield role and synthesis pathway of LPS, which have attracted considerable attention to discover molecules able to surmount antibiotic resistance, either circumventing LPS defenses or disrupting its synthesis. We specifically focus on the enhanced sampling and free energy calculation methods that have been combined with MD simulations to address such research. We also highlight the use of special-purpose MD supercomputers, the importance of appropriate LPS and ions parameterization to obtain reliable results, and the complementary views that MD and wet-lab experiments provide. Thereby, this work, which covers the last five years of research, apart from outlining the phenomena and strategies that are being explored, evidences the valuable insights that are gained by MD, which may be useful to advance antibiotic design, and what the prospects of this in silico method could be in LPS research.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10902/26996
url https://hdl.handle.net/10902/26996
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Computational and Structural Biotechnology Journal, 2022, 20, 5886-5901
reponame:UCrea Repositorio Abierto de la Universidad de Cantabria
instname:Universidad de Cantabria (UC)
instname_str Universidad de Cantabria (UC)
reponame_str UCrea Repositorio Abierto de la Universidad de Cantabria
collection UCrea Repositorio Abierto de la Universidad de Cantabria
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869407753690152960
score 15.300719

Similares en LA Referencia