scholarly journals The Lazy Life of Lipid-Linked Oligosaccharides in All Life Domains

2019 ◽  
Author(s):  
Pablo Ricardo Arantes ◽  
Conrado Pedebos ◽  
Marcelo D. Poleto ◽  
Laércio Pol-Fachin ◽  
Hugo Verli
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Membrane Lipid ◽  
Membrane Dynamics ◽  
En Bloc ◽  
Future Studies ◽  
Head Groups ◽  
Domains Of Life ◽  
Glycosylation Pathway ◽  
Dynamics Simulations

<div> <div> <div> <p>Lipid-linked oligosaccharides (LLOs) plays an important role in the N-glycosylation pathway as the donor substrate of oligosaccharyltransferases (OSTs), which are respon- sible for the en bloc transfer of glycan chains onto a nascent polypeptide. The lipid component of LLO in both eukarya and archaea consists of a dolichol, and an unde- caprenol in prokarya, whereas the number of isoprene units may change between species. Given the potential relevance of LLOs and their related enzymes to diverse biotechno- logical applications, obtaining reliable LLO models from distinct domains of life could support further studies on complex formation and their processing by OSTs, as well as protein engineering on such systems. In this work, molecular modeling, such as quantum mechanics calculations, molecular dynamics simulations, and metadynamics were employed to study eukaryotic (Glc3-Man9-GlcNAc2-PP-Dolichol), bacterial (Glc1- GalNAc5-Bac1-PP-Undecaprenol) and archaeal (Glc1-Man1-Gal1-Man1-Glc1-Gal1-Glc1- P-Dolichol) LLO in membrane bilayers. Microsecond molecular dynamics simulations and metadynamics calculations of LLOs revealed that glycan chains are more prone to interact with the membrane lipid head groups, while the PP linkages are positioned at the lipid phosphate head groups level. Dynamics of isoprenoid chains embedded within the bilayer are described and membrane dynamics and its related properties are also investigated. Overall, there are similarities regarding the structural and dynamics of the eukaryotic, the bacterial and the archaeal LLOs in bilayers, which can support the comprehension of their association with OSTs. This data may support future studies on the transferring mechanism of the oligosaccharide chain to an acceptor protein. </p> </div> </div> </div>

scholarly journals The Lazy Life of Lipid-Linked Oligosaccharides in All Life Domains

2019 ◽  
Author(s):  
Pablo Ricardo Arantes ◽  
Conrado Pedebos ◽  
Marcelo D. Poleto ◽  
Laércio Pol-Fachin ◽  
Hugo Verli
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Membrane Lipid ◽  
Membrane Dynamics ◽  
En Bloc ◽  
Future Studies ◽  
Head Groups ◽  
Domains Of Life ◽  
Glycosylation Pathway ◽  
Dynamics Simulations

<div> <div> <div> <p>Lipid-linked oligosaccharides (LLOs) plays an important role in the N-glycosylation pathway as the donor substrate of oligosaccharyltransferases (OSTs), which are respon- sible for the en bloc transfer of glycan chains onto a nascent polypeptide. The lipid component of LLO in both eukarya and archaea consists of a dolichol, and an unde- caprenol in prokarya, whereas the number of isoprene units may change between species. Given the potential relevance of LLOs and their related enzymes to diverse biotechno- logical applications, obtaining reliable LLO models from distinct domains of life could support further studies on complex formation and their processing by OSTs, as well as protein engineering on such systems. In this work, molecular modeling, such as quantum mechanics calculations, molecular dynamics simulations, and metadynamics were employed to study eukaryotic (Glc3-Man9-GlcNAc2-PP-Dolichol), bacterial (Glc1- GalNAc5-Bac1-PP-Undecaprenol) and archaeal (Glc1-Man1-Gal1-Man1-Glc1-Gal1-Glc1- P-Dolichol) LLO in membrane bilayers. Microsecond molecular dynamics simulations and metadynamics calculations of LLOs revealed that glycan chains are more prone to interact with the membrane lipid head groups, while the PP linkages are positioned at the lipid phosphate head groups level. Dynamics of isoprenoid chains embedded within the bilayer are described and membrane dynamics and its related properties are also investigated. Overall, there are similarities regarding the structural and dynamics of the eukaryotic, the bacterial and the archaeal LLOs in bilayers, which can support the comprehension of their association with OSTs. This data may support future studies on the transferring mechanism of the oligosaccharide chain to an acceptor protein. </p> </div> </div> </div>

Dynamics of Membrane-Embedded Lipid-Linked Oligosaccharides for the Three Domains of Life

2019 ◽  
Author(s):  
Pablo Ricardo Arantes ◽  
Conrado Pedebos ◽  
Laércio Pol-Fachin ◽  
Marcelo D. Poleto ◽  
Hugo Verli
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Membrane Surface ◽  
Membrane Lipid ◽  
Head Group ◽  
En Bloc ◽  
Structure And Dynamics ◽  
Domains Of Life ◽  
Dynamics Simulations ◽  
Orientation Structure

<div>Lipid-linked oligosaccharides (LLOs) are the substrates of oligosaccharyltransferases (OSTs), enzymes that catalyze the en bloc transfer of a glycan chain during the process of N-glycosylation. LLOs are composed by an isoprenoid chain moiety and an oligosaccharide, linked by one or more pyrophosphate groups (PP). The lipid component on LLO is a dolichol in eukarya and archaea, and an undecaprenol in prokarya, whereas the number of isoprene units may change between species. Given the potential relevance of LLOs and their metabolizing enzymes to diverse biotechnological applications, LLOs’ models from different domains of life in their native conditions could support further studies of their complexation and processing by OSTs, as well as protein engineering on such systems. Accordingly, the GROMOS53A6 force field was employed, added by GROMOS53a6GLYC parameters for the saccharidic moiety. The torsional parameters for the isoprenoid portion were derived from a fit to the proper quantum mechanical potential energy profiles at the HF 6-31G* and validated against experimental condensed phase properties. Molecular dynamics simulations employed GROMACS package to access the orientation, structure, and dynamics of eukaryotic (Glc3-Man9-GlcNAc2-PP-Dolichol), bacterial (Glc1-GalNAc5-Bac1-PP-Undecaprenol) and archaeal (Glc1-Man1-Gal1-Man1-Glc1-Gal1-Glc1-P-Dolichol) LLO in membrane bilayers. Microsecond molecular dynamics simulations of LLOs revealed that most carbohydrate residues interact with the membrane lipid head groups, parallel to the membrane surface, while the PP linkages are within the lipid head group, and the isoprenoid chains are within the bilayer. Overall, there are similarities in the orientations, structure, and dynamics of the eukaryotic, bacterial and archaea LLOs in bilayers. LLOs’ preferred orientation, structure and dynamics provided information for complexation with OSTs, allowing further studies of how these enzymes catalyze the transfer of the oligosaccharide chain to an acceptor protein by OSTs.</div>

scholarly journals Membrane potential and dynamics in a ternary lipid mixture: insights from molecular dynamics simulations

2018 ◽  
Vol 20 (23) ◽  
pp. 15841-15851 ◽  
Author(s):  
Xubo Lin ◽  
Vinay Nair ◽  
Yong Zhou ◽  
Alemayehu A. Gorfe
Keyword(s):  
Molecular Dynamics ◽  
Membrane Potential ◽  
Molecular Dynamics Simulations ◽  
Transmembrane Potential ◽  
Lipid Mixture ◽  
Structure And Dynamics ◽  
Head Groups ◽  
Acyl Chains ◽  
Dynamics Simulations

Transmembrane potential modulates the structure and dynamics of lipid head-groups and acyl chains.

scholarly journals Evidence from molecular dynamics simulations of conformational preorganization in the ribonuclease H active site

F1000Research ◽  
2014 ◽  
Vol 3 ◽  
pp. 67 ◽  
Author(s):  
Kate A. Stafford ◽  
Arthur G. Palmer III
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Active Site ◽  
Extensive Study ◽  
Rnase H ◽  
Dynamic Feature ◽  
Magnesium Ions ◽  
E Coli ◽  
Domains Of Life ◽  
Dynamics Simulations

Ribonuclease H1 (RNase H) enzymes are well-conserved endonucleases that are present in all domains of life and are particularly important in the life cycle of retroviruses as domains within reverse transcriptase. Despite extensive study, especially of the E. coli homolog, the interaction of the highly negatively charged active site with catalytically required magnesium ions remains poorly understood. In this work, we describe molecular dynamics simulations of the E. coli homolog in complex with magnesium ions, as well as simulations of other homologs in their apo states. Collectively, these results suggest that the active site is highly rigid in the apo state of all homologs studied and is conformationally preorganized to favor the binding of a magnesium ion. Notably, representatives of bacterial, eukaryotic, and retroviral RNases H all exhibit similar active-site rigidity, suggesting that this dynamic feature is only subtly modulated by amino acid sequence and is primarily imposed by the distinctive RNase H protein fold.

scholarly journals Atomistic Molecular Dynamics Simulations of Trioleoylglycerol – Phospholipid Membrane Systems

2020 ◽  
Author(s):  
Mirza Ahmed Hammad ◽  
Hafiza Minal Akram ◽  
Muhammad Sohail Raza
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Lipid Droplets ◽  
Membrane System ◽  
Bilayer Membrane ◽  
Coarse Grained ◽  
Phospholipid Membrane ◽  
Software Suite ◽  
Future Studies ◽  
Dynamics Simulations

AbstractAdiposomes are phospholipid coated triacylglyceride particles that serve as structural models of the fat storage compartments of cells, known as lipid droplets (LDs); however, unlike LDs, they do not carry proteins. There is a deficit of available methods and experimental data regarding the internal packing of the adiposomes, and computer simulations offer a promising way to pinpoint the molecular arrangements within these structures. However, in the absence of a triacylglycerol-specific atomic forcefield, thus far, all adiposome/LD simulations have been performed with the coarse grained/united atom forcefields. Yet it is desirable to model the phospholipid/triacylglycerol interface with atomic resolution. In the present study, we first prepared a 2-monooleoylglycerol (MOG) forcefield which was then used to build a trioleoylglycerol (TOG) forcefield by the modular approach of the AMBER software suite. TOG bilayer membrane (2L) systems were modelled from two different initial conformations; TOG3 and TOG2:1. The simulations revealed that TOG2:1 is the most populated conformation in TOG membranes, irrespective of the starting conformation. Some other parameter optimizations were performed for TOG membranes based on which adiposome mimicking tetralayer membrane system (4L) was prepared with a TOG bilayer at core surrounded by two DOPC leaflets. The 4L membranes were stable throughout the simulations, however it was observed that a small amount of cations and water diffused from surface to the TOG core of the membrane. Based on these results a TAG-packing model was also developed. It is expected that the availability of MOG forcefield will equip future studies with a framework for molecular dynamics simulations of adiposomes/LDs.

scholarly journals Molecular Dynamics Simulations of Bacterial Outer Membrane Lipid Extraction: Adequate Sampling?

2020 ◽  
Author(s):  
Jonathan Shearer ◽  
Jan K. Marzinek ◽  
Peter J. Bond ◽  
Syma Khalid
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Outer Membrane ◽  
Lipid Extraction ◽  
Membrane Lipid ◽  
Computational Effort ◽  
Potential Of Mean Force ◽  
Coarse Grained ◽  
Adequate Sampling ◽  
Dynamics Simulations

AbstractThe outer membrane of Gram-negative bacteria is almost exclusively composed of lipopolysaccharide in its outer leaflet, whereas the inner leaflet contains a mixture of phospholipids. Lipopolysaccharide diffuses at least an order of magnitude slower than phospholipids, which can cause issues for molecular dynamics simulations in terms of adequate sampling. Here we test a number of simulation protocols for their ability to achieve convergence with reasonable computational effort using the MARTINI coarse-grained force-field. This is tested in the context both of potential of mean force (PMF) calculations for lipid extraction from membranes, and of lateral mixing within the membrane phase. We find that decoupling the cations that cross-link the lipopolysaccharide headgroups from the extracted lipid during PMF calculations is the best approach to achieve convergence comparable to that for phospholipid extraction. We also show that lateral lipopolysaccharide mixing/sorting is very slow and not readily addressable even with Hamiltonian replica exchange. We discuss why more sorting may be unrealistic for the short (microseconds) timescales we simulate and provide an outlook for future studies of lipopolysaccharide-containing membranes.

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