You want to visualize protein-ligand unpaired and clash interactions. See example in Figure 1.
The DepictUnpairedMap illustrates how simple it is to generate these images.
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def depict_unpairedmap(image, protein, ligand, opts): # perceive interactions asite = oechem.OEInteractionHintContainer(protein, ligand) if not asite.IsValid(): oechem.OEThrow.Fatal("Cannot initialize active site!") asite.SetTitle(ligand.GetTitle()) oechem.OEPerceiveInteractionHints(asite) # depiction oegrapheme.OEPrepareActiveSiteDepiction(asite) adisp = oegrapheme.OE2DActiveSiteDisplay(asite, opts) oegrapheme.OERenderUnpairedInteractionMap(image, adisp)
prompt > wget https://files.rcsb.org/download/1nq2.pdb prompt > python3 unpairedmap2img.py -complex 1nq2.pdb -out 1nq2.svg
Currently the OEPerceiveInteractionHints function perceives the following interaction types:
¶ name corresponding interaction class corresponding interaction type namespace cation-pi OECationPiInteractionHint OECationPiInteractionHintType chelator OEChelatorInteractionHint OEChelatorInteractionHintType clash OEClashInteractionHint None contact OEContactInteractionHint None covalent OECovalentInteractionHint None halogen bond OEHalogenBondInteractionHint OEHalogenBondInteractionHintType hydrogen bond OEHBondInteractionHint OEHBondInteractionHintType salt-bridge OESaltBridgeInteractionHint OESaltBridgeInteractionHintType stacking (T and Pi) OEStackingInteractionHint OEStackingInteractionHintType
The default geometric parameters used by the OEPerceiveInteractionHints function have been set based on literature data ([Kumar-2002], [Cavallo-2016], [Bissantz-2010], and [Marcou-2007] ). The interaction parameters can be customized by using the OEPerceiveInteractionOptions class.
Atom clash interaction
When visualizing protein-ligand atom crashes, red outline of a residue circle indicates that there are one or more atoms in that residue which are too close to some ligand atom(s). Clashing ligand atoms are marked with a red arc that is directed towards the corresponding clashing residue. The red shading on the grey line representing the shape of the pocket is used to identify atom clashes easily.
Unpaired types of the hydrogen bonding interaction
An unpaired hydrogen bond interaction is detected:
Different linker types are used to mark unpaired acceptor and donor hydrogen bond interactions. Please note that since these interactions are unpaired, the direction of the linkers has no real spatial meaning. Ligand linkers are directed away from the ligand, while protein linkers are directed towards the ligand.
|unpaired ligand acceptor||unpaired protein acceptor||unpaired ligand donor||unpaired protein donor|
Clash types of the hydrogen bonding interaction
A hydrogen bond clash interaction is detected:
|donor-donor clash||acceptor-acceptor clash|
Unpaired types of the salt-bridge interaction
An unpaired salt bridge interaction is detected if there is a positively / negatively charged functional group either in the ligand or in nearby protein without a matching negatively / positively charged functional group, respectively.
Different linker types are used to mark unpaired positive and negative salt-bridge interactions. Please note that since these interactions are unpaired, the direction of the linkers has no real spatial meaning. Ligand linkers are directed away from the ligand, while protein linkers are directed towards the ligand.
|unpaired ligand positive||unpaired protein positive||unpaired ligand negative||unpaired protein negative|
Since the interaction perception dependents on the position of hydrogens, it is highly recommended to optimize those positions prior to perceiving the interactions. The two images below reveal the effect of optimizing the hydrogen bond network in a protein-ligand complex: less atom clash(es) and less unpaired hydrogen bond interaction(s).
|original complex downloaded from PDB Database (PDB 1D3H)||complex after optimizing hydrogen positions|
An unpaired interaction map provides a complementary view to the more common active site interaction map. While the interaction map (on the right) depicts interactions between the ligand and protein, the unpaired map (on the left) illustrates interactions that could contribute to binding but are not formed in the complex. Together, these two maps of the protein-ligand binding site provide insights into protein-ligand interactions and communicate complex 3D structural results to medicinal chemists in a directly actionable way.
|unpaired interaction map (PDB 1BR6)||active site interaction map (PDB 1BR6)|