Assessing the Role of Electrostatic Interactions in the Mechanism of Beta-Barrel Channel Gating

AbstractDifferential geometry (DG) based solvation models have shown their great success in solvation analysis by avoiding the use of ad hoc surface definitions, coupling the polar and nonpolar free energies, and generating solvent-solute boundary in a physically self-consistent fashion. Parameter optimization is a key factor for their accuracy, predictive ability of solvation free energies, and other applications. Recently, a series of efforts have been made to improve the parameterization of these new implicit solvent models. In thiswork, we aim at studying the role of dispersion attraction in the parameterization of our DG based solvation models. To this end, we first investigate the necessity of van derWaals (vdW) dispersion interactions in the model and then carry out systematic parameterization for the model in the absence of electrostatic interactions. In particular, we explore how the changes in Lennard-Jones (L-J) potential expression, its decomposition scheme, and choices of some fixed parameter values affect the optimal values of other parameters as well as the overall modeling error. Our study on nonpolar solvation analysis offers insights into the parameterization of nonpolar components for the full DG based models by eliminating uncertainties from the electrostatic polar component. Therefore, it can be regarded as a step towards better parameterization for the full DG based model.

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Solvent effect on the conformational behavior of substituted spiro[4.5]decanes and spiro[5.5]undecanes

Canadian Journal of Chemistry ◽

10.1139/v95-089 ◽

1995 ◽

Vol 73 (5) ◽

pp. 703-709 ◽

Cited By ~ 6

Author(s):

S. Sağ Erdem ◽

T. Varnali ◽

V. Aviyente ◽

M.F. Ruiz-Lopez

Keyword(s):

Solvent Effect ◽

Electrostatic Interactions ◽

Multipole Moment ◽

Semiempirical Methods ◽

Main Role ◽

Solvent Interactions ◽

Reaction Field ◽

Solvent Models ◽

Conformational Equilibria

We studied the relatively complex polar systems 6-substituted-1,4-dioxospiro[4.5]decanes and 7-substituted-1,5-dioxospiro[5.5]undecanes with substituents X = CH3, F, Cl, CN, OH, OCH3, and NO2. Solvent effects on the equilibrium have been analysed by means of a Self-Consistent-Reaction-Field model and the PM3 method. Complete geometry optimizations have been carried out for all the structures in the gas phase and in solution. For some substituents, a set of rotamers have been separately optimized. The discussion of the results is focussed on the effects arising from structural aspects and from steric and electrostatic interactions on the axial/equatorial relative stability. The role played by multipole moment is considered. In general, good agreement with available experimental data and with previous theoretical studies has been obtained. Though the use of semiempirical methods and simple solvent models prevents us from reaching definitive conclusions, this approach seems to be very useful in predicting the main role of solute–solvent interactions in conformational equilibria of complex systems for which ab initio calculations cannot be performed. Keywords: conformational equilibria, spiro decanes and undecanes, cavity model, SCRF, solvent effect, PM3 calculations.

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The role of BamA in the biogenesis of beta-barrel membrane proteins

Acta Crystallographica Section A Foundations and Advances ◽

10.1107/s2053273314094212 ◽

2014 ◽

Vol 70 (a1) ◽

pp. C578-C578

Author(s):

Nicholas Noinaj ◽

Adam Kuszak ◽

Curtis Balusek ◽

JC Gumbart ◽

Petra Lukacik ◽

...

Keyword(s):

Membrane Proteins ◽

Outer Membrane ◽

Crystal Structures ◽

Outer Membrane Proteins ◽

Hydrophobic Surface ◽

Md Simulations ◽

Structural Features ◽

Bam Complex ◽

Beta Barrel

Beta-barrel membrane proteins are essential for nutrient import, signaling, motility, and survival. In Gram-negative bacteria, the beta-barrel assembly machinery (BAM) complex is responsible for the biogenesis of beta-barrel outer membrane proteins (OMPs), with homologous complexes found in mitochondria and chloroplasts. Despite their essential roles, exactly how these OMPs are formed remains unknown. The BAM complex consists of a central and essential component called BamA (an OMP itself) and four lipoproteins called BamB-E. While the structure of the lipoproteins have been reported, the structure of full length BamA has been elusive. Recently though, we described the structure of BamA from two species of bacteria: Neisseria gonorrhoeae and Haemophilus ducreyi. BamA consists of a large periplasmic domain attached to a 16-strand transmembrane beta-barrel domain. Together, our crystal structures and molecule dynamics (MD) simulations revealed several structural features which gave clues to the mechanism by which BamA catalyzes beta-barrel assembly. The first is that the interior cavity is accessible in one BamA structure and conformationally closed in the other. Second, an exterior rim of the beta-barrel has a distinctly narrowed hydrophobic surface, locally destabilizing the outer membrane. Third, the beta-barrel can undergo lateral opening, suggesting a route from the interior cavity in BamA into the outer membrane. And fourth, a surface exposed exit pore positioned above the lateral opening site which may play a role in the biogenesis of extracellular loops. In this presentation, the crystal structures and MD simulations of BamA will be presented along with our work looking at the role of these four structural features in the role of BamA within the BAM complex.

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Binding From both sides: TolR and full-length OmpA bind and maintain the local structure of the E. coli cell wall

10.1101/409466 ◽

2018 ◽

Cited By ~ 1

Author(s):

Alister T. Boags ◽

Firdaus Samsudin ◽

Syma Khalid

Keyword(s):

Cell Wall ◽

Electrostatic Interactions ◽

Cell Envelope ◽

Binding Domain ◽

Gram Negative Bacteria ◽

Inner Membrane ◽

E Coli ◽

Non Covalent Interactions ◽

Covalent Interactions

SUMMARYWe present a molecular modeling and simulation study of the of the E. coli cell envelope, with a particular focus on the role of TolR, a native protein of the E. coli inner membrane in interactions with the cell wall. TolR has been proposed to bind to peptidoglycan, but the only structure of this protein thus far is in a conformation in which the putative peptidoglycan binding domain is not accessible. We show that a model of the extended conformation of the protein in which this domain is exposed, binds peptidoglycan largely through electrostatic interactions. We show that non-covalent interactions of TolR and OmpA with the cell wall, from the inner membrane and outer membrane sides respectively, maintain the position of the cell wall even in the absence of Braun’s lipoprotein. When OmpA is truncated to remove the peptidoglycan binding domain, TolR is able to pull the cell wall down towards the inner membrane. The charged residues that mediate the cell-wall interactions of TolR in our simulations, are conserved across a number of species of Gram-negative bacteria.

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