Molecular dynamics simulation of six β-blocker drugs passing across POPC bilayer

<div><p>Six selected β-blocker drugs (alprenolol, atenolol, metoprolol, nadolol, pindolol and propranolol) passing across 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayer were studied using all-atom molecular dynamics simulation. The free energy profiles can be divided into two groups, according to their shapes: the free energy curve of group one (atenolol, nadolol and pindolol) has an obvious minimum while that of the other group (propranolol, metoprolol and alprenolol) is flat inside membrane. Energy analysis shows that electrostatic interaction plays an important role for the first group drugs. The hydrogen bond analysis results also certify that the first group drugs form more hydrogen bonds than the other β-blockers. The calculated permeability sequence agrees with the experimental ones. Our calculation suggests that the permeability model using potential of mean force (PMF) method can be also applied to chemically similar compounds besides chemically diverse compounds.</p></div

Insights into the binding of agonist and antagonist to TAS2R16 receptor: a molecular simulation study

<p>The human bitter taste receptors (TAS2Rs) belong to the GPCR family, while the activation mechanism and how TAS2Rs recognise bitter ligands are poorly understood. In this study, 3D structure of TAS2R16 was constructed using homology modelling complemented with molecular dynamics method. Salicin and probenecid were docked to TAS2R16 receptor to investigate the possible activation mechanism of TAS2R16. The results show that salicin and probenecid locate at the binding pocket made up of transmembrane helices TM3, TM5 and TM7, and the second and third extracellular loops ECL2 and ECL3. Structural analysis reveals that the network interactions at the third intracellular loop ICL3 may play a crucial role in stabilising the inactive state of TAS2R16, and structural change in the intracellular region is correlated with the activation of TAS2R16. The binding energies of salicin and probenecid to TAS2R16 are −152.81 ± 15.09 and −271.90 ± 26.97 kJ/mol, respectively, indicating that a potential antagonist should have obviously stronger binding affinity.</p

Predicted monomeric structure (A) and Ramachandran plot (B) of Lhβ-defensin.

<p>Predicted monomeric structure (A) and Ramachandran plot (B) of Lhβ-defensin.</p

Reduced density gradient isosurface and residue type of Lhβ-defensin dimer.

<p>(A) Reduced density gradient isosurface map between Arg54 and Tyr32 in dimeric structure of Lhβ-defensin created by Multiwfn software [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0157544#pone.0157544.ref036" target="_blank">36</a>]. The blue, red and green (or earth green) colors indicate the strong attractive, strong repulsive and van der Waals interaction, respectively. (B) Surface of dimer colored by residue type. Blue are basic residues, red are acidic residues, green are polar residues, and white are non-polar residues.</p

Tissues expression of Lhβ-defensin in tissues of healthy and <i>S</i>. <i>dysgalactiae</i> infected fish.

<p>(A) Expression of Lhβ-defensin in healthy fish was measured by realtime PCR and normalized to β-actin. (B) Expression of Lhβ-defensin in fish infected with <i>S</i>. <i>dysgalactiae</i>. Fish in the bacterial infected group were infected intraperitoneally with 2×10⁶ CFU live <i>S</i>. <i>dysgalactiae</i> and the control group was injected with the same amount of PBS solution. At 24 hpi, the tissues were selected for the gene expression analysis by Realtime PCR method. Asterisks indicate that the expression of Lhβ-defensin in the infected group was significantly up-regulated compared with that of control group (*<i>P</i><0.05).</p

Multiple alignment of vertebrates β-defensins.

<p>C1-C6 indicated the six conserved cysteine residues. Black shade indicated identical amino acids and gray shade indicated similar amino acids.</p

Snapshot showing the water defects and water translocations across the membrane (A); Interactions between arginines of Lhβ-defensin and POPG bilayer (B).

<p>Snapshot showing the water defects and water translocations across the membrane (A); Interactions between arginines of Lhβ-defensin and POPG bilayer (B).</p

Order parameters (S_CD) of saturated (sn-1) and unsaturated (sn-2) hydrocarbon chains in POPG computed using the last 20 ns trajectories of stimulation.

<p>Sn-1 and sn-2 referred to S_CD calculated by POPG in the presence of Lhβ-defensin dimer, sn1-local and sn2-local to S_CD calculated when PGPG was around 10 Å of defensin dimer, while sn1-pure POPG and sn2-pure POPG to S_CD calculated by POPG in the absence of Lhβ-defensin dimer.</p

Regioselective Deacetylation of Peracetylated Deoxy‑<i>C</i>‑glycopyranosides by Boron Trichloride (BCl₃)

A general approach for regioselective deacetylation at sugar 3-OH of peracetylated 6-deoxy-C-glucopyranosides mediated by BCl3 was developed. The approach could be extended to other sugar-derived 6-deoxy-C-glycopyranosides, such as those derived from mannose, galactose, and rhamnose, with deacetylation occurring at varied sugar hydroxyl groups, and further extended to 4-deoxy-C-glucopyranosides with deacetylation occurring at sugar 3-OH. The approach would enable access to synthetically challenging carbohydrate derivatives. A possible mechanism of the regioselectivity was proposed