scholarly journals Interactions of Truncated Menaquinones in Lipid Monolayers and Bilayers

2021 ◽  
Vol 22 (18) ◽  
pp. 9755
Author(s):  
Cameron Van Cleave ◽  
Jordan T. Koehn ◽  
Caroline Simões Pereira ◽  
Allison A. Haase ◽  
Benjamin J. Peters ◽  
...  
Keyword(s):  
Membrane System ◽  
Md Simulations ◽  
Model Membrane ◽  
Transport Systems ◽  
Side Chain ◽  
Interfacial Water ◽  
Physiological Conditions ◽  
Cellular Energy ◽  
Fundamental Information ◽  
Location Association

Menaquinones (MK) are hydrophobic molecules that consist of a naphthoquinone headgroup and a repeating isoprenyl side chain and are cofactors used in bacterial electron transport systems to generate cellular energy. We have previously demonstrated that the folded conformation of truncated MK homologues, MK-1 and MK-2, in both solution and reverse micelle microemulsions depended on environment. There is little information on how MKs associate with phospholipids in a model membrane system and how MKs affect phospholipid organization. In this manuscript, we used a combination of Langmuir monolayer studies and molecular dynamics (MD) simulations to probe these questions on truncated MK homologues, MK-1 through MK-4 within a model membrane. We observed that truncated MKs reside farther away from the interfacial water than ubiquinones are are located closer to the phospholipid tails. We also observed that phospholipid packing does not change at physiological pressure in the presence of truncated MKs, though a difference in phospholipid packing has been observed in the presence of ubiquinones. We found through MD simulations that for truncated MKs, the folded conformation varied, but MKs location and association with the bilayer remained unchanged at physiological conditions regardless of side chain length. Combined, this manuscript provides fundamental information, both experimental and computational, on the location, association, and conformation of truncated MK homologues in model membrane environments relevant to bacterial energy production.

A Model Membrane System to Investigate Antioxidants in Bovine Rod Outer Segments

1997 ◽  
Vol 64 (3) ◽  
pp. 313-321 ◽  
Author(s):  
SUSAN A. KEYS ◽  
ELENA BOLEY ◽  
WILLIAM F. ZIMMERMAN
Keyword(s):  
Membrane System ◽  
Model Membrane ◽  
Rod Outer Segments ◽  
Outer Segments

Membrane transport systems. II. Transport of alkali metal ions against their concentration gradients

1981 ◽  
Vol 59 (12) ◽  
pp. 1734-1744 ◽  
Author(s):  
Thomas M. Fyles ◽  
Virginia A. Malik-Diemer ◽  
Dennis M. Whitfield
Keyword(s):  
Alkali Metal ◽  
Metal Ions ◽  
Metal Ion ◽  
Complex Function ◽  
Membrane System ◽  
Ion Concentration ◽  
Transport Systems ◽  
Alkali Metal Ions ◽  
Concentration Gradients ◽  
Membrane Transport Systems

An artificial membrane system based on a series of macrocyclic polyether carriers (crown ethers) is described. Under the influence of a proton gradient the carriers move alkali metal ions from basic to acidic solution through a chloroform membrane phase. Transport occurs against the concentration gradient of the transported ion as a result of a coupled counterflow of protons. Different transport behaviors are observed depending upon the metal ion concentration. At high metal ion concentration the amount transported is a linear function of time; at lower metal ion concentration the amount transported is a complex function of time which may be described as the result of a pair of consecutive first order processes. Effects of metal ion, carrier, and proton concentration on transport rate are considered. The rate increases with increasing metal ion or carrier concentration but is essentially independent of the pH of either aqueous phase. Increased lipophilicity of the carrier also results in a rate increase. Carriers derived from 18-crown-6 transport potassium selectively and all ions more rapidly than 15-crown-5 derivatives which are, however, selective for sodium. The overall efficiency of the system is discussed in terms of competing "leak" reactions, either of cations from the basic phase or of anions from the acidic phase.

The diffusion of ions from a phospholipid model membrane system

PROTOPLASMA ◽  
1967 ◽  
Vol 63 (1-3) ◽  
pp. 183-187 ◽  
Author(s):  
A. D. Bangham ◽  
M. M. Standish ◽  
J. C. Watkins ◽  
G. Weissmann
Keyword(s):  
Membrane System ◽  
Model Membrane

scholarly journals The role of side chains in the interaction of new antitumor pyrimidoacridinetriones with DNA: molecular dynamics simulations.

2000 ◽  
Vol 47 (1) ◽  
pp. 47-57 ◽  
Author(s):  
J Mazerski ◽  
I Antonini ◽  
S Martelli
Keyword(s):  
Molecular Dynamics ◽  
Rational Design ◽  
Md Simulations ◽  
Ring System ◽  
Side Chain ◽  
Side Chains ◽  
Intercalation Complex ◽  
Highly Active ◽  
Simulation Techniques ◽  
Dynamics Simulations

Pyrimidoacridinetriones (PATs) are a new group of highly active antitumor compounds. It seems reasonable to assume that, like for some other acridine derivatives, intercalation into DNA is a necessary, however not a sufficient condition for antitumor activity of these compounds. Rational design of new compounds of this chemotype requires knowledge about the structure of the intercalation complex, as well as about interactions responsible for its stability. Computer simulation techniques such as molecular dynamics (MD) may provide valuable information about these problems. The results of MD simulations performed for three rationally selected PATs are presented in this paper. The compounds differ in the number and position of side chains. Each of the compounds was simulated in two systems: i) in water, and ii) in the intercalation complex with the dodecamer duplex d(GCGCGCGCGCGC)2. The orientation of the side chain in relation to the ring system is determined by the position of its attachment. Orientation of the ring system inside the intercalation cavity depends on the number and position of side chain(s). The conformations of the side chain(s) of all PATs studied in the intercalation complex were found to be very similar to those observed in water.

scholarly journals Novel Pyrazolo[3,4-c]pyridine Antagonists with Nanomolar affinity for A1 / A3 Adenosine Receptors: Binding Kinetics and Exploration of their Binding Profile Using Mutagenesis Experiments, MD simulations and TI/MD calculations

2021 ◽  
Author(s):  
Margarita Stampelou ◽  
Anna Suchankova ◽  
Eva Tzortzini ◽  
Lakshiv Dhingra ◽  
Kerry Barkan ◽  
...  
Keyword(s):  
Drug Design ◽  
Transmembrane Helix ◽  
Rank Correlation ◽  
Membrane System ◽  
Md Simulations ◽  
Dissociation Rate ◽  
The Novel ◽  
Free Energies ◽  
Electronegative Group ◽  
Good Agreement

Drugs targeting the four adenosine receptor (AR) subtypes can provide “soft" treatment of various significant diseases. Even for the two experimentally resolved AR subtypes the description of the orthosteric binding area and structure-activity relationships of ligands remains a demanding task due to the high similar amino acids sequence but also the broadness and flexibility of the ARs binding area. The identification of new pharmacophoric moieties and nanomolar leads and the exploration of their binding area with mutagenesis and state-of-the-art computational methods useful also for drug design purposes remains a challenging aim for all ARs. Here, we identified several low nanomolar ligands and potent competitive antagonists against A1R / A3R, containing the novel pyrazolo[3,4-c]pyridine pharmacophore for ARs, from a screen of an in-house library of only 52 compounds, originally designed for anti-proliferative activity. We identified L2-L10, A15, A17 with 3-aryl, 7-anilino and a electronegative group at 5-position as low micromolar to low nanomolar A1R / A3R antagonists. A17 has for A1R Kd = 5.62 nM and a residence time (RT) 41.33 min and for A3R Kd = 13.5 nM, RT = 47.23 min. The kinetic data showed that compared to the not potent or mediocre congeners the active compounds have similar association, for example at A1R Kon = 13.97 x106 M-1 (A17) vs Kon = 3.36 x106 M-1 (A26) but much lower dissociation rate Koff = 0.024 min-1 (A17) vs 0.134 min-1 (A26). Using molecular dynamics (MD) simulations and mutagenesis experiments we investigated the binding site of A17 showing that it can interact with an array of residues in transmembrane helix 5 (TM5), TM6, TM7 of A1R or A3R including residues E5.30, E5.28, T7.35 in A1R instead of Q5.28, V5.30 , L7.35 in A3R. A striking observation for drug design purposes is that for L2506.51A the binding affinity of A17 significantly increased at A1R. A17 provides a lead representative of a promising series and by means of the Thermodynamics Integration coupled with MD simulations (TI/MD) method, first applied here on whole GPCR- membrane system and showing a very good agreement between calculated and experimental relative binding free energies for A1R and A3R (spearman rank correlation p = 0.82 and 0.84, respectively), and kinetic experiments can lead to ligands with improved profile against ARs.

The Diffusion of Ions from a Phospholipid Model Membrane System

1967 ◽  
pp. 183-187 ◽  
Author(s):  
A. D. Bangham ◽  
M. M. Standish ◽  
J. C. Watkins ◽  
G. Weissmann
Keyword(s):  
Membrane System ◽  
Model Membrane

scholarly journals Influence of Calcium Binding on Conformations and Motions of Anionic Polyamino Acids. Effect of Side Chain Length

Polymers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1279
Author(s):  
Dmitry Tolmachev ◽  
Natalia Lukasheva ◽  
George Mamistvalov ◽  
Mikko Karttunen
Keyword(s):  
Amino Acids ◽  
Chain Length ◽  
Calcium Binding ◽  
Md Simulations ◽  
Side Chain ◽  
Replica Exchange ◽  
Side Chain Length ◽  
Hamiltonian Replica Exchange ◽  
Cacl2 Concentration ◽  
Chain Lengths

Investigation of the effect of CaCl2 salt on conformations of two anionic poly(amino acids) with different side chain lengths, poly-(α-l glutamic acid) (PGA) and poly-(α-l aspartic acid) (PASA), was performed by atomistic molecular dynamics (MD) simulations. The simulations were performed using both unbiased MD and the Hamiltonian replica exchange (HRE) method. The results show that at low CaCl2 concentration adsorption of Ca2+ ions lead to a significant chain size reduction for both PGA and PASA. With the increase in concentration, the chains sizes partially recover due to electrostatic repulsion between the adsorbed Ca2+ ions. Here, the side chain length becomes important. Due to the longer side chain and its ability to distance the charged groups with adsorbed ions from both each other and the backbone, PGA remains longer in the collapsed state as the CaCl2 concentration is increased. The analysis of the distribution of the mineral ions suggests that both poly(amino acids) should induce the formation of mineral with the same structure of the crystal cell.

Deuterium NMR study of the effect of n- anesthetics on a model membrane system

1985 ◽  
Vol 817 (2) ◽  
pp. 355-365 ◽  
Author(s):  
Jenifer L. Thewalt ◽  
Stephen R. Wassall ◽  
Heiner Gorrissen ◽  
Robert J. Cushley
Keyword(s):  
Membrane System ◽  
Model Membrane ◽  
Deuterium Nmr ◽  
Nmr Study

Interactions of the aluminum(III) ion in a model membrane system

1983 ◽  
Vol 105 (15) ◽  
pp. 4901-4905 ◽  
Author(s):  
Alan S. Tracey ◽  
Taryn L. Boivin
Keyword(s):  
Membrane System ◽  
Model Membrane
Sign in / Sign up

Export Citation Format

Share Document