Molecular dynamics modeling of the Vibrio cholera Na+-translocating NADH:quinone oxidoreductase NqrB–NqrD subunit interface

AbstractThe Na+-translocating NADH:quinone oxidoreductase (Na+-NQR) is the major Na+ pump in aerobic pathogens such as Vibrio cholerae. The interface between two of the NQR subunits, NqrB and NqrD, has been proposed to harbor a binding site for inhibitors of Na+-NQR. While the mechanisms underlying Na+-NQR function and inhibition remain underinvestigated, their clarification would facilitate the design of compounds suitable for clinical use against pathogens containing Na+-NQR. An in silico model of the NqrB–D interface suitable for use in molecular dynamics simulations was successfully constructed. A combination of algorithmic and manual methods was used to reconstruct portions of the two subunits unresolved in the published crystal structure and validate the resulting structure. Hardware and software optimizations that improved the efficiency of the simulation were considered and tested. The geometry of the reconstructed complex compared favorably to the published V. cholerae Na+-NQR crystal structure. Results from one 1 µs, three 150 ns and two 50 ns molecular dynamics simulations illustrated the stability of the system and defined the limitations of this model. When placed in a lipid bilayer under periodic boundary conditions, the reconstructed complex was completely stable for at least 1 µs. However, the NqrB–D interface underwent a non-physiological transition after 350 ns.

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Molecular dynamics modeling ofPseudomonas aeruginosaouter membranes

Physical Chemistry Chemical Physics ◽

10.1039/c8cp04278k ◽

2018 ◽

Vol 20 (36) ◽

pp. 23635-23648 ◽

Cited By ~ 12

Author(s):

Ao Li ◽

Jeffrey W. Schertzer ◽

Xin Yong

Keyword(s):

Molecular Dynamics ◽

Pseudomonas Aeruginosa ◽

Molecular Dynamics Simulations ◽

Lipid Membranes ◽

Structural Information ◽

Dynamics Modeling ◽

Biologically Relevant ◽

Molecular Dynamics Modeling ◽

Dynamics Simulations

All-atom molecular dynamics simulations provide important structural information of asymmetric lipid membranes that are biologically relevant toPseudomonas aeruginosa.

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Combined Use of Structure Analysis, Studies of Molecular Association in Solution, and Molecular Modelling to Understand the Different Propensities of Dihydroxybenzoic Acids to Form Solid Phases

Pharmaceutics ◽

10.3390/pharmaceutics13050734 ◽

2021 ◽

Vol 13 (5) ◽

pp. 734

Author(s):

Aija Trimdale ◽

Anatoly Mishnev ◽

Agris Bērziņš

Keyword(s):

Crystal Structure ◽

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

Structure Analysis ◽

Crystal Structure Analysis ◽

Molecular Association ◽

Hydroxyl Groups ◽

Solid Phases ◽

Solvent Molecules ◽

Dynamics Simulations

The arrangement of hydroxyl groups in the benzene ring has a significant effect on the propensity of dihydroxybenzoic acids (diOHBAs) to form different solid phases when crystallized from solution. All six diOHBAs were categorized into distinctive groups according to the solid phases obtained when crystallized from selected solvents. A combined study using crystal structure and molecule electrostatic potential surface analysis, as well as an exploration of molecular association in solution using spectroscopic methods and molecular dynamics simulations were used to determine the possible mechanism of how the location of the phenolic hydroxyl groups affect the diversity of solid phases formed by the diOHBAs. The crystal structure analysis showed that classical carboxylic acid homodimers and ring-like hydrogen bond motifs consisting of six diOHBA molecules are prominently present in almost all analyzed crystal structures. Both experimental spectroscopic investigations and molecular dynamics simulations indicated that the extent of intramolecular bonding between carboxyl and hydroxyl groups in solution has the most significant impact on the solid phases formed by the diOHBAs. Additionally, the extent of hydrogen bonding with solvent molecules and the mean lifetime of solute–solvent associates formed by diOHBAs and 2-propanol were also investigated.

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