Out of Sight, Out of Mind: The Effect of the Equilibration Protocol on the Structural Ensembles of Charged Glycolipid Bilayers

Messias, Andresa; Santos, Denys E. S.; Pontes, Frederico J. S.; Lima, Filipe da Silva; Soares, Thereza A.

doi:10.3390/molecules25215120

Cited by 10 publications

(4 citation statements)

References 55 publications

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“…The full system was again geometry-optimized with the steepest descent algorithm. The system was slowly thermalized through five simulations in the NVT ensemble, at 100, 150, 200, 250, and 300 K, each with 5,000,000 steps . The temperature was kept constant by applying a velocity-rescaling thermostat with a coupling constant of 0.4 ps .…”

Section: Methodsmentioning

confidence: 99%

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Exploring the Molecular Dynamics of a Lipid-A Vesicle at the Atom Level: Morphology and Permeation Mechanism

et al. 2023

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Lipid-A was previously shown to spontaneously aggregate into a vesicle via the hybrid particle field approach. We assess the validity of the proposed vesiculation mechanism by simulating the resulting lipid-A vesicle at the atom level. The spatial confinement imposed by the vesicle geometry on the conformation and packing of lipid-A induces significant heterogeneity of physical properties in the inner and outer leaflets. It also induces tighter molecular packing and lower acyl chain order compared to the lamellar arrangement. Around 5% of water molecules passively permeates the vesicle membrane inward and outward. The permeation is facilitated by interactions with water molecules that are transported across the membrane by a network of electrostatic interactions with the hydrogen bond donors/acceptors in the N-acetylglucosamine ring and upper region of the acyl chains of lipid-A. The permeation process takes place at low rates but still at higher frequencies than observed for the lamellar arrangement of lipid-A. These findings not only substantiate the proposed lipid-A vesiculation mechanism but also reveal the complex structural dynamics of an important nonlamellar arrangement of lipid-A.

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Section: Methodsmentioning

confidence: 99%

“…The system was slowly thermalized through five simulations in the NVT ensemble, at 100, 150, 200, 250, and 300 K, each with 5,000,000 steps. 42 The temperature was kept constant by applying a velocity-rescaling thermostat with a coupling constant of 0.4 ps. 43 Each of the equilibration steps was performed using the leapfrog integrator.…”

Section: Methodsmentioning

confidence: 99%

Exploring the Molecular Dynamics of a Lipid-A Vesicle at the Atom Level: Morphology and Permeation Mechanism

et al. 2023

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“…This recommended order (NVT followed by NPT equilibration) in the Gromacs tutorial (http://www.mdtutorials.com/gmx/lysozyme/07 _equil2.html, accessed on 22 November 2023) supposedly results in fast thermal equilibration in the NVT step, which can then be followed by pressure equilibration in the NPT step. For biological systems, it is observed that with the absence of the NVT step, enormous pressures may develop at the onset of the NPT step, pushing around water molecules into non-physical locations [49].…”

Section: Methodsmentioning

confidence: 99%

Collagen Structured Hydration

Biswal,

Agmon

2023

Biomolecules

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Collagen is a triple-helical protein unique to the extracellular matrix, conferring rigidity and stability to tissues such as bone and tendon. For the [(PPG)10]3 collagen-mimetic peptide at room temperature, our molecular dynamics simulations show that these properties result in a remarkably ordered first hydration layer of water molecules hydrogen bonded to the backbone carbonyl (bb-CO) oxygen atoms. This originates from the following observations. The radius of gyration attests that the PPG triplets are organized along a straight line, so that all triplets (excepting the ends) are equivalent. The solvent-accessible surface area (SASA) for the bb-CO oxygens shows a repetitive regularity for every triplet. This leads to water occupancy of the bb-CO sites following a similar regularity. In the crystal-phase X-ray data, as well as in our 100 K simulations, we observe a 0-2-1 water occupancy in the P-P-G triplet. Surprisingly, a similar (0-1.7-1) regularity is maintained in the liquid phase, in spite of the sub-nsec water exchange rates, because the bb-CO sites rarely remain vacant. The manifested ordered first-shell water molecules are expected to produce a cylindrical electrostatic potential around the peptide, to be investigated in future work.

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“…Note that this work was partially motivated by a recent simulation study by Amy et al that explored the influence of the protonation states of lipid A glucosamine phosphate groups on the properties of bilayers composed of Salmonella enterica lipid A and Rc core (two Kdo (2-keto-3-deoxyoctulosonate), three Hep, and one Glc ( d -glucose)) . Among much recent progress in MD simulations of various LPS systems, − their study is the first work (to the best of our knowledge) to investigate the different phosphate protonation states and LPS-ion interactions.…”

Section: Introductionmentioning

confidence: 99%

CHARMM-GUI Supports Hydrogen Mass Repartitioning and Different Protonation States of Phosphates in Lipopolysaccharides

Gao

Lee

Smith

et al. 2021

J. Chem. Inf. Model.

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Hydrogen mass repartitioning (HMR) that permits time steps of all-atom molecular dynamics simulation up to 4 fs by increasing the mass of hydrogen atoms has been used in protein and phospholipid bilayers simulations to improve conformational sampling. Molecular simulation input generation via CHARMM-GUI now supports HMR for diverse simulation programs. In addition, considering ambiguous pH at the bacterial outer membrane surface, different protonation states, either -2e or -1e, of phosphate groups in lipopolysaccharides (LPS) are also supported in CHARMM-GUI LPS Modeler. To examine the robustness of HMR and the influence of protonation states of phosphate groups on LPS bilayer properties, eight different LPS-type all-atom systems with two phosphate protonation states are modeled and simulated utilizing both OpenMM 2-fs (standard) and 4-fs (HMR) schemes. Consistence in the conformational space sampled by standard and HMR simulations shows the reliability of HMR even in LPS, one of the most complex biomolecules. For systems with different protonation states, similar conformations are sampled with a PO4 1or PO4 2group, but different phosphate protonation states make slight impacts on lipid packing and conformational properties of LPS acyl chains. Systems with PO4 1have slightly smaller area per lipid and thus slightly more ordered lipid A acyl chains compared to those with PO4 2-, due to more electrostatic repulsion between PO4 2even with neutralizing Ca 2+ ions. HMR and different protonation states of phosphates of LPS available in CHARMM-GUI are expected to be useful for further investigations of biological systems of diverse origin.

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Out of Sight, Out of Mind: The Effect of the Equilibration Protocol on the Structural Ensembles of Charged Glycolipid Bilayers

Cited by 10 publications

References 55 publications

Exploring the Molecular Dynamics of a Lipid-A Vesicle at the Atom Level: Morphology and Permeation Mechanism

Exploring the Molecular Dynamics of a Lipid-A Vesicle at the Atom Level: Morphology and Permeation Mechanism

Collagen Structured Hydration

CHARMM-GUI Supports Hydrogen Mass Repartitioning and Different Protonation States of Phosphates in Lipopolysaccharides

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