The most probable trajectory for ion flux through large-pore channel

Bransburg-Zabary, Sharron; Nachliel, Esther; Gutman, Menachem

doi:10.1016/j.ssi.2003.02.003

Cited by 4 publications

(3 citation statements)

References 28 publications

(35 reference statements)

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“…2(a)]. The narrowing contributes to selective passage of molecules and determines ions conductivity 30. As can be seen from Figure 2, HOLE and MolAxis agree on the results and both find an almost identical path with a similar running time of about 5 s. The radius at the narrowest point is 3.9 Å and the corresponding residues are Y96 and the negatively‐charged D90 on one side and the positively charged R32 on the opposite side.…”

Section: Resultssupporting

confidence: 66%

MolAxis: Efficient and accurate identification of channels in macromolecules

et al. 2008

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Channels and cavities play important roles in macromolecular functions, serving as access/exit routes for substrates/products, cofactor and drug binding, catalytic sites, and ligand/protein. In addition, channels formed by transmembrane proteins serve as transporters and ion channels. MolAxis is a new sensitive and fast tool for the identification and classification of channels and cavities of various sizes and shapes in macromolecules. MolAxis constructs corridors, which are pathways that represent probable routes taken by small molecules passing through channels. The outer medial axis of the molecule is the collection of points that have more than one closest atom. It is composed of two-dimensional surface patches and can be seen as a skeleton of the complement of the molecule. We have implemented in MolAxis a novel algorithm that uses state-of-the-art computational geometry techniques to approximate and scan a useful subset of the outer medial axis, thereby reducing the dimension of the problem and consequently rendering the algorithm extremely efficient. MolAxis is designed to identify channels that connect buried cavities to the outside of macromolecules and to identify transmembrane channels in proteins. We apply MolAxis to enzyme cavities and transmembrane proteins. We further utilize MolAxis to monitor channel dimensions along Molecular Dynamics trajectories of a human Cytochrome P450. MolAxis constructs high quality corridors for snapshots at picosecond time-scale intervals substantiating the gating mechanism in the 2e substrate access channel. We compare our results with previous tools in terms of accuracy, performance and underlying theoretical guarantees of finding the desired pathways. MolAxis is available on line as a web-server and as a standalone easy-to-use program (http://bioinfo3d.cs.tau.ac.il/MolAxis/).

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Section: Resultssupporting

confidence: 66%

MolAxis: Efficient and accurate identification of channels in macromolecules

et al. 2008

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“…The surface conductivity of bacterial cells can be highly affected by specific activity of certain membrane proteins under extreme ionic strength conditions. Mechanosensitive channels in the inner membrane play an important role in ionic transfer during hypoosmotic shock to avoid cell lysis. , Several outer membrane proteins (Omp), such as OmpF, a large pore channel, allow ionic exchanges between the periplasm and the bulk solution by electrodiffusion. , The release of co-ions by the cells due to the accumulation of counterions in the double layer in proximity of the core surface allows maintenance of a constant transmembrane potential and osmotic pressure. Hence, additional factors related to the cell membrane activity need to be taken into account when extreme ionic conditions are employed during EPM measurements of bacterial cells.…”

Section: Resultsmentioning

confidence: 99%

Relevance of Electrokinetic Theory for “Soft” Particles to Bacterial Cells: Implications for Bacterial Adhesion

2005

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Bacterial cells and other biological particles carry charged macromolecules on their surface that form a "soft" ion-permeable layer. In this paper, we test the applicability of an electrokinetic theory for soft particles to characterize the electrophoretic mobility (EPM) and adhesion kinetics of bacterial cells. The theory allows the calculation of two parameters--the electrophoretic softness and the fixed charged density--that define the characteristics of the polyelectrolyte layer at the soft particle surface. The theory also allows the calculation of an outer-surface potential that may better predict the electrostatic interaction of soft particles with solid surfaces. To verify its relevance for bacterial cells, the theory was applied to EPM measurements of two well-characterized Escherichia coli K12 mutants having lipopolysaccharide (LPS) layers of different lengths and molecular compositions. Results showed that the obtained softness and fixed charge density were not directly related to the known characteristics of the LPS of the selected strains. Interaction energy profiles calculated from Derjaguin-Landau-Verwey-Overbeek (DLVO) theory were used to interpret bacterial deposition (adhesion) rates on a pure quartz surface. The outer surface potential failed to predict the low attachment efficiencies of the two bacterial strains. The lack of success in the application of the theory for soft particles to bacterial cells is attributed to chemical and physical heterogeneities of the polyelectrolyte layer at the cell surface.

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“…34͒ or other methods. 64,65 Next, we investigated if, in addition to screening possible conformations of the solute in the pore, the G-SMD method can adequately describe permeation kinetics and relative translocation velocities. For this purpose we carried out G-SMD simulations on DNA strands of different sequences and global orientations.…”

Section: Discussionmentioning

confidence: 99%

Exploring transmembrane transport through α-hemolysin with grid-steered molecular dynamics

Wells

Abramkina

Aksimentiev

2007

The Journal of Chemical Physics

133

186

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The transport of biomolecules across cell boundaries is central to cellular function. While structures of many membrane channels are known, the permeation mechanism is known only for a select few. Molecular dynamics (MD) is a computational method that can provide an accurate description of permeation events at the atomic level, which is required for understanding the transport mechanism. However, due to the relatively short time scales accessible to this method, it is of limited utility. Here, we present a method for all-atom simulation of electric field-driven transport of large solutes through membrane channels, which in tens of nanoseconds can provide a realistic account of a permeation event that would require a millisecond simulation using conventional MD. In this method, the average distribution of the electrostatic potential in a membrane channel under a transmembrane bias of interest is determined first from an all-atom MD simulation. This electrostatic potential, defined on a grid, is subsequently applied to a charged solute to steer its permeation through the membrane channel. We apply this method to investigate permeation of DNA strands, DNA hairpins, and alpha-helical peptides through alpha-hemolysin. To test the accuracy of the method, we computed the relative permeation rates of DNA strands having different sequences and global orientations. The results of the G-SMD simulations were found to be in good agreement in experiment.

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The most probable trajectory for ion flux through large-pore channel

Cited by 4 publications

References 28 publications

MolAxis: Efficient and accurate identification of channels in macromolecules

MolAxis: Efficient and accurate identification of channels in macromolecules

Relevance of Electrokinetic Theory for “Soft” Particles to Bacterial Cells: Implications for Bacterial Adhesion

Exploring transmembrane transport through α-hemolysin with grid-steered molecular dynamics

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