ROCS.

<p>Receiver operating characteristic curve comparison against selected query molecules used for structral similarity.</p

Comparison of various FLAP-pharmacophore models.

<p>Note: H: Shape, O: Hydrogen bond acceptor, N1: Hydrogen bond donor, DRY: Hydrophobic, Glob-Prod: Global Product scores, Glob_Sum: Global Sum score, AUC: Area under curve.</p

FLAP Models.

<p>Panel A. Pseudomolecule (Pharmacophoric atoms) shown (left) in gray/blue/red spheres with aligned molecules (wire representation), modified model 1 (right). GRID 3D molecule interaction fields (MIFs) of models are shown as follows: The green contours correspond to the DRY probe (energy level −0.63 kcal/mol), blue contours correspond to the N1 probe (energy level −3.83 kcal/mol) and red contours correspond to the O probe (energy level −1.50 kcal/mol). Panel B. Enrichment plot of screening for 20 known actives from 971 inactive compounds from the PubChem database. Enrichment plot of model 1–4 (left), Enrichment plot of modified model 1–4 (right).</p

Pharmacophore hypothesis.

<p>Schematic representation of hypothesis 1 (left panel) and hypothesis 2 (right panel) for HIV-1 RT associated RNase H inhibitors. The metal ions chelation of N-hydroxyimides is shown in orange with distances measured by Klumpp et al.</p

HIV-1 RT associated RNase H model and ligands structures.

<p>Panel A: The model of HIV-RT associated RNase H domain is shown with a bound ligand (cyan, ball and stick model). The catalytically important residues, magnesium ions (green sphere) and bound water (cyan sphere) have been highlighted. The docking pose of the bound ligand is shown in pink (ball and stick model), Panel B: 2D representation of ligand-protein interaction. Panel C: Representative molecules belong to the class of site directed RNase H inhibition.</p

The overall workflow of the present study.

<p>The overall workflow of the present study.</p

Comparison of the pharmacophore model with docking experiment.

<p>Panel A. First ranked docking poses superimposed with the pharmacophore (Hypothesis 1, AAAR). Panel B. The first ranked docking pose is shown in the active site of RNase H and important residues are highlighted, including magnesium ions (green sphere) and water (cyan sphere).</p

Validation of active subsets as a reference molecule for similarity search.

<p>Validation of active subsets as a reference molecule for similarity search.</p

Summary of enrichment factor estimation from various docking scenarios.

<p>Note: ROC = Receiver Operator Characterics, XP: Extra precision, SP: Standard precision, HTS: High throughput screening.</p

Shape and pharmacophore.

<p>The best query molecules from ROC validation are shown with hydrogen bonding donor (cyan), hydrogen-bonding acceptors (red), rings (green) and negatively charged (blue) features.</p