Jaguar input files

Jaguar input files for geometry optimization of halobenzene...NMA complexes starting from an ideal halogen bond geometry

Binding-affinity predictions of HSP90 in the D3R Grand Challenge 2015 with docking, MM/GBSA, QM/MM, and free-energy simulations

We have estimated the binding affinity of three sets of ligands of the heat-shock protein 90 in the D3R grand challenge blind test competition. We have employed four different methods, based on five different crystal structures: first, we docked the ligands to the proteins with induced-fit docking with the Glide software and calculated binding affinities with three energy functions. Second, the docked structures were minimised in a continuum solvent and binding affinities were calculated with the MM/GBSA method (molecular mechanics combined with generalised Born and solvent-accessible surface area solvation). Third, the docked structures were re-optimised by combined quantum mechanics and molecular mechanics (QM/MM) calculations. Then, interaction energies were calculated with quantum mechanical calculations employing 970–1160 atoms in a continuum solvent, combined with energy corrections for dispersion, zero-point energy and entropy, ligand distortion, ligand solvation, and an increase of the basis set to quadruple-zeta quality. Fourth, relative binding affinities were estimated by free-energy simulations, using the multi-state Bennett acceptance-ratio approach. Unfortunately, the results were varying and rather poor, with only one calculation giving a correlation to the experimental affinities larger than 0.7, and with no consistent difference in the quality of the predictions from the various methods. For one set of ligands, the results could be strongly improved (after experimental data were revealed) if it was recognised that one of the ligands displaced one or two water molecules. For the other two sets, the problem is probably that the ligands bind in different modes than in the crystal structures employed or that the conformation of the ligand-binding site or the whole protein changes

Main methods and tools for peptide development based on protein-protein interactions (PPIs)

Protein-protein interactions (PPIs) regulate crucial physiological and pathological processes. PPIs are considered a class of biological targets almost infeasible for small molecules because the binding surfaces are usually large and shallow. Peptides are molecules able to bind to these drug targets; they can be used as modulators and mimic one of the interaction partners. This review details the advances in in silico peptide design and experimental approaches for the evaluation of PPI-based peptides

L'Auto-vélo : automobilisme, cyclisme, athlétisme, yachting, aérostation, escrime, hippisme / dir. Henri Desgranges

09 juillet 19421942/07/09 (A43,N15163)

Averaged H-bond (first four columns) and π-stacking interaction (last two columns) distances for the ligand-PDE3A complexes extracted from molecular docking experiments.^a.

<p>Averaged H-bond (first four columns) and π-stacking interaction (last two columns) distances for the ligand-PDE3A complexes extracted from molecular docking experiments.<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0189213#t001fn001" target="_blank">^a</a>.</p

Statistical information of FQSAR models.^a.

<p>Statistical information of FQSAR models.<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0189213#t002fn001" target="_blank">^a</a>.</p

Scatter plots of the experimental vs. predicted activities for the best FQSAR models.

<p>Plots are shown for alignments PPA, PA, and DA. (●) training, (○) LOO cross-validated, (×) test set predictions, and solid line is for x = y.</p

Superposition of PDE3A model (pale orange) to the PDE3B crystal structure (cyan).

<p>(a) Protein structure visualization presenting modeled loops (L1 and L2), and the location of metal and ligand binding site. (b) Comparison of PDE 3A/3B active sites; tertiary protein structure is shown in ribbons, relevant protein residues and water molecules are shown as thick tubes, magnesium ions are shown as van der Waals spheres, and ligands are shown in ball-and-stick representation; dotted lines indicate zero-order bonds, dashed black lines represent H-bonds, and cyan dashed lines indicate π-stacking interactions. Carbon coloring are: cyan and light blue for protein and ligand atoms in the PDE3B crystal, and pale orange and orange for protein and ligand atoms in the PDE3A model.</p

Structure of PDE3A inhibitor series.

<p>Common chemical scaffolds among the studied compounds are shown. Pyrazolopyridine and pyridazinone/pyrazolone moieties are highlighted in orange and magenta, respectively.</p