iPHACE
integrative navigation in pharmacological space
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Drug/Target spaces

There are three icons on the top-left side of both Drug and Target Space working areas. The actions linked to them are:

  • Reloads the application
  • Shows the Interaction map corresponding to the selected node
  • Hops from Drug Space to its associated Target Space and viceversa

In the Drug Space, there are three additional icons on the top-right side of the working area. The actions linked to them are:

  • Shows all frameworks under the selected node
  • Shows all scaffolds under the selected node
  • Shows all molecules under the selected node

Still in the Drug space, there are three links that give you access to chemical structure information, namely, frameworks, scaffolds, and molecules of the working drug set. Clicking on one of those links will load the corresponding structures in the Structural browser. In the Target space, this place is reserved to display the number of targets and the number or target families of the working target set.

Drug Space is currently composed of 739 drugs and is organised using a six-level structural hierarchy (Curr Top Med Chem 2005; 5: 763): the top three levels are integers representing the number of rings in the largest ring system, the number of ring systems, and the number of bonds connecting the most distant ring systems in the structure, respectively; the remaining three levels are hash-codes that uniquely identify the atomic framework, the scaffold, and finally the molecule, respectively. In turn, Target Space is currently composed of 181 targets and is organised using standard functional classification schemes available for G protein-coupled receptors (GR) and ion channels (IC).

In Drug Space, additional information is displayed for each node of the structural hierarchy:

  • Hierarchy level: It is an integer for the first three levels and an image of the correponding structure for the framework and scaffold levels
  • Affinity bar: Affinity values, expressed as -log(molar), are associated with the strength of the interaction between a drug and a target. The bar is divided in five sections related to affinity ranges - <=6, (6;7], (7;8], (8;9], >9 - and the color of each section reflects the percentage of interaction data in that node with affinity values within the corresponding range, white being 0% and dark red being 100%. Some illustrative examples are provided below:
    • ll interaction data for the drugs contained in this node have values under 6. This is thus a “low affinity” node
    • ll interaction data for the drugs contained in this node have values over 8, most of them being in the range (8,9] and some of them with values over 9. This is thus a “high affinity” node
  • Ligand Efficiency bar: Efficiency values provide a measure of the affinity per molecular weight unit (pActivity / MW) and thus allow for assessing whether drugs have an optimal balance between target potency and molecular size. The bar is divided in five sections related to efficiency ranges - <=12, (12,24], (24,36], (36,48], >48 - and the color of each section reflects the percentage of drugs in that node with efficiency values within the corresponding range, white being 0% and dark red being 100%.
  • Population bar: Population values give the number of drugs contained within each node. The length of the bar provides an intuitive idea of the relative population of drugs within the different nodes. In addition, placing the mouse over the population bar displays the number of drugs contained in the node, whereas placing the mouse aside the population bar displays the number of hierarchical sublevels linked to the node.
  • View molecules icon: Once the scaffold level is reached, clicking on this icon activates the visualisation of structures in the Structural browser for all drugs containing that scaffold.

In Target Space, additional information is displayed once the final target level is reached:

  • Hop icon: allows for hopping to the drug space linked to a particular target. Effectively acts as a target filter.
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