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...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Computational and Structural Biotechnology Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S200103702200486X |
| _version_ | 1797978168583258112 |
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| author | Cristina González-Fernández Eugenio Bringas Chris Oostenbrink Inmaculada Ortiz |
| author_facet | Cristina González-Fernández Eugenio Bringas Chris Oostenbrink Inmaculada Ortiz |
| author_sort | Cristina González-Fernández |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T05:18:41Z |
| format | Article |
| id | doaj.art-ac486106144042f6911046ae0b181421 |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-04-11T05:18:41Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-ac486106144042f6911046ae0b1814212022-12-24T04:54:58ZengElsevierComputational and Structural Biotechnology Journal2001-03702022-01-012058865901In silico investigation and surmounting of Lipopolysaccharide barrier in Gram-Negative Bacteria: How far has molecular dynamics Come?Cristina González-Fernández0Eugenio Bringas1Chris Oostenbrink2Inmaculada Ortiz3Department of Chemical and Biomolecular Engineering, ETSIIT, University of Cantabria, Avda. Los Castros s/n, 39005 Santander, SpainDepartment of Chemical and Biomolecular Engineering, ETSIIT, University of Cantabria, Avda. Los Castros s/n, 39005 Santander, SpainInstitute for Molecular Modeling and Simulation, BOKU – University of Natural Resources and Life Sciences, Muthgasse 18, 1190 Vienna, AustriaDepartment of Chemical and Biomolecular Engineering, ETSIIT, University of Cantabria, Avda. Los Castros s/n, 39005 Santander, Spain; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S200103702200486XLipopolysaccharide (LPS)Antibiotic resistanceMolecular dynamics (MD)Enhanced samplingFree energy calculationSpecial-purpose MD supercomputers |
| spellingShingle | Cristina González-Fernández Eugenio Bringas Chris Oostenbrink Inmaculada Ortiz In silico investigation and surmounting of Lipopolysaccharide barrier in Gram-Negative Bacteria: How far has molecular dynamics Come? Computational and Structural Biotechnology Journal Lipopolysaccharide (LPS) Antibiotic resistance Molecular dynamics (MD) Enhanced sampling Free energy calculation Special-purpose MD supercomputers |
| title | 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_short | 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 |
| topic | Lipopolysaccharide (LPS) Antibiotic resistance Molecular dynamics (MD) Enhanced sampling Free energy calculation Special-purpose MD supercomputers |
| url | http://www.sciencedirect.com/science/article/pii/S200103702200486X |
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