scholarly journals Glucose transport via the pseudomonad porin OprB: implications for the design of Trojan Horse anti-infectives

2019 ◽  
Vol 21 (16) ◽  
pp. 8457-8463 ◽  
Author(s):  
Joan Coines ◽  
Silvia Acosta-Gutierrez ◽  
Igor Bodrenko ◽  
Carme Rovira ◽  
Matteo Ceccarelli
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Glucose Transport ◽  
Trojan Horse ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Dynamical Features ◽  
Dynamics Simulations

Knowing the structural and dynamical features of specific porins from poor-permeable Gram-negative bacteria helps to design anti-infectives with optimal permeation. Molecular dynamics simulations can characterize and quantify the transport of substrates through these specific porins.

The membranes of Gram-negative bacteria: progress in molecular modelling and simulation

2015 ◽  
Vol 43 (2) ◽  
pp. 162-167 ◽  
Author(s):  
Syma Khalid ◽  
Nils A. Berglund ◽  
Daniel A. Holdbrook ◽  
Yuk M. Leung ◽  
Jamie Parkin
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Lipid Bilayers ◽  
Molecular Modelling ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Bacterial Membranes ◽  
Lipid Species ◽  
Membrane Models ◽  
Dynamics Simulations

Molecular modelling and simulations have been employed to study the membranes of Gram-negative bacteria for over 20 years. Proteins native to these membranes, as well as antimicrobial peptides and drug molecules have been studied using molecular dynamics simulations in simple models of membranes, usually only comprising one lipid species. Thus, traditionally, the simulations have reflected the majority of in vitro membrane experimental setups, enabling observations from the latter to be rationalized at the molecular level. In the last few years, the sophistication and complexity of membrane models have improved considerably, such that the heterogeneity of the lipid and protein composition of the membranes can now be considered both at the atomistic and coarse-grain levels of granularity. Importantly this means relevant biology is now being retained in the models, thereby linking the in silico and in vivo scenarios. We discuss recent progress in simulations of proteins in simple lipid bilayers, more complex membrane models and finally describe some efforts to overcome timescale limitations of atomistic molecular dynamics simulations of bacterial membranes.

scholarly journals Plasticity within the barrel domain of BamA mediates a hybrid-barrel mechanism by BAM

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Runrun Wu ◽  
Jeremy W. Bakelar ◽  
Karl Lundquist ◽  
Zijian Zhang ◽  
Katie M. Kuo ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Single Unit ◽  
Outer Membrane Proteins ◽  
Conformational Dynamics ◽  
Accessory Proteins ◽  
Gram Negative Bacteria ◽  
Folding Intermediate ◽  
Gram Negative ◽  
Dynamics Simulations

AbstractIn Gram-negative bacteria, the biogenesis of β-barrel outer membrane proteins is mediated by the β-barrel assembly machinery (BAM). The mechanism employed by BAM is complex and so far- incompletely understood. Here, we report the structures of BAM in nanodiscs, prepared using polar lipids and native membranes, where we observe an outward-open state. Mutations in the barrel domain of BamA reveal that plasticity in BAM is essential, particularly along the lateral seam of the barrel domain, which is further supported by molecular dynamics simulations that show conformational dynamics in BAM are modulated by the accessory proteins. We also report the structure of BAM in complex with EspP, which reveals an early folding intermediate where EspP threads from the underside of BAM and incorporates into the barrel domain of BamA, supporting a hybrid-barrel budding mechanism in which the substrate is folded into the membrane sequentially rather than as a single unit.

scholarly journals Insight into the Structure and Dynamics of Polymers by Neutron Scattering Combined with Atomistic Molecular Dynamics Simulations

Polymers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3067
Author(s):  
Arantxa Arbe ◽  
Fernando Alvarez ◽  
Juan Colmenero
Keyword(s):  
Molecular Dynamics ◽  
Neutron Scattering ◽  
Molecular Dynamics Simulations ◽  
Structural Features ◽  
Length Scales ◽  
Polymeric Systems ◽  
Structure And Dynamics ◽  
Dynamical Features ◽  
Dynamics Simulations ◽  
Insight Into

Combining neutron scattering and fully atomistic molecular dynamics simulations allows unraveling structural and dynamical features of polymer melts at different length scales, mainly in the intermolecular and monomeric range. Here we present the methodology developed by us and the results of its application during the last years in a variety of polymers. This methodology is based on two pillars: (i) both techniques cover approximately the same length and time scales and (ii) the classical van Hove formalism allows easily calculating the magnitudes measured by neutron scattering from the simulated atomic trajectories. By direct comparison with experimental results, the simulated cell is validated. Thereafter, the information of the simulations can be exploited, calculating magnitudes that are experimentally inaccessible or extending the parameters range beyond the experimental capabilities. We show how detailed microscopic insight on structural features and dynamical processes of various kinds has been gained in polymeric systems with different degrees of complexity, and how intriguing questions as the collective behavior at intermediate length scales have been faced.

Insights into structural and dynamical features of water at halloysite interfaces probed by DFT and classical molecular dynamics simulations

2016 ◽  
Vol 18 (3) ◽  
pp. 2164-2174 ◽  
Author(s):  
Davide Presti ◽  
Alfonso Pedone ◽  
Giordano Mancini ◽  
Celia Duce ◽  
Maria Rosaria Tiné ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Density Functional ◽  
Density Functional Theory Calculations ◽  
Water Molecules ◽  
Functional Theory ◽  
Structure And Dynamics ◽  
Classical Molecular Dynamics ◽  
Dynamical Features ◽  
Dynamics Simulations

Density functional theory calculations and classical molecular dynamics simulations have been used to investigate the structure and dynamics of water molecules on kaolinite surfaces and confined in the interlayer of a halloysite model of nanometric dimension.

scholarly journals Progress in Molecular Dynamics Simulations of Gram-Negative Bacterial Cell Envelopes

2017 ◽  
Vol 8 (11) ◽  
pp. 2513-2518 ◽  
Author(s):  
Alister Boags ◽  
Pin-Chia Hsu ◽  
Firdaus Samsudin ◽  
Peter J. Bond ◽  
Syma Khalid
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Bacterial Cell ◽  
Gram Negative ◽  
Dynamics Simulations ◽  
Cell Envelopes

scholarly journals The Hitchhiker’s Guide to the Periplasm: Unexpected Molecular Interactions of Antibiotics Revealed by Considering Crowding Effects in E. coli

2020 ◽  
Author(s):  
Conrado Pedebos ◽  
Iain P. S. Smith ◽  
Alister Boags ◽  
Syma Khalid
Keyword(s):  
Molecular Dynamics ◽  
Antibacterial Agents ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
E Coli ◽  
Crowding Effects ◽  
Therapeutic Mechanism ◽  
Target Membrane ◽  
Dynamics Simulations ◽  
Crowded Environment

AbstractThe periplasm of Gram-negative bacteria is a highly crowded environment comprised of many different molecular species. Antibacterial agents that causes lysis of Gram-negative bacteria by their action against the inner membrane must cross the periplasm to arrive at their target membrane. Very little is currently known about their route through the periplasm, and the interactions they experience. To this end, here atomistic molecular dynamics simulations are used to study the path taken by the antibiotic polymyxin B1 through a number of models of the periplasm which are crowded with proteins and osmolytes to different extents. The simulations reveal that PMB1 forms transient and long-lived interactions with proteins and osmolytes that are free in solution as well as lipoproteins anchored to the outer membrane and bound to the cell wall. We show that PMB1 may be able to ‘hitchhike’ within the periplasm by binding to lipoprotein carriers. Overall our results show that PMB1 is rarely uncomplexed within the periplasm; an important consideration for interpretations of its therapeutic mechanism of action. It is likely that this observation can be extended to other antibiotics that rely on diffusion to cross the periplasm.

Single glucose molecule transport process revealed by force tracing and molecular dynamics simulations

2018 ◽  
Vol 3 (5) ◽  
pp. 517-524 ◽  
Author(s):  
Yangang Pan ◽  
Yuebin Zhang ◽  
Pianchou Gongpan ◽  
Qingrong Zhang ◽  
Siteng Huang ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Glucose Transport ◽  
Single Molecule ◽  
Transport Process ◽  
Theoretical Methods ◽  
Molecule Transport ◽  
Glucose Molecule ◽  
Dynamics Simulations

Single-molecule glucose transport was illuminated using both experimental and theoretical methods.

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