Interaction Perception

OEBio TK provides the following APIs to perceive protein-ligand interactions:

OEPerceiveInteractionHints

The function that perceives protein-ligand interactions.

OEPerceiveInteractionOptions

The class that stores the parameters that control the interaction perception.

The default geometric parameters have been set based on literature data ([Kumar-2002], [Cavallo-2016], [Bissantz-2010], and [Marcou-2007] ).

Interaction Hint Container

Interactions perceived by the OEPerceiveInteractionHints function are stored in an OEInteractionHintContainer object. The architecture of the OEInteractionHintContainer class is depicted in Schematic representation of interaction hint container.

../_images/interactionhint.svg

Schematic representation of interaction hint container

OEInteractionHintContainer

This is the main container that stores typed molecules (OEMolBase), fragments of those molecules (OEInteractionHintFragment) and typed interactions (OEInteractionHint) between the fragments.

OEInteractionHintComponentTypeBase

The abstract class that enables to type molecules stored in the interaction container. Each molecule added to the container has to have a specific type. Currently, there are two built-in component types available:

OEInteractionHintFragment

Set of atoms of a molecule that is stored in the interaction container. These are the atoms that are contribute to an interaction (OEInteractionHint). Some interactions, such as hydrogen bonds, are between two atoms; other ones define interactions between set of atoms. For example, a stacking interaction is between atoms of two aromatic ring systems.

OEInteractionHint

An iteration is defined between two fragments (OEInteractionHintFragment) stored in the container. An interaction can be either inter (OEInteractionHint.IsInter) or intra (OEInteractionHint.IsIntra) molecular. Each interaction has a specific type that is derived from the OEInteractionHintTypeBase class.

OEInteractionHintTypeBase

The abstract class that enables to type interactions stored in the interaction container. The table below shows the specific interaction types currently available in OEBio TK. Some interaction classes are also associated with namespaces that enable to subtype the main interaction types. For example, the stacking interaction have two subtypes:

Interaction types currently available in OEBio TK

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

Other related APIs:

OEIsValidActiveSite

This function checks whether the interaction container initialized correctly as active site i.e. containing two molecules: one typed as ligand and one typed as protein.

OEGetActiveSiteInteractionHintTypes

This function iterates over all interaction types (including subtypes) that are perceived by the OEPerceiveInteractionHints function.

Code Examples

Interaction Hint Predicates

The table below list all interaction predicates that are currently available in OEBio TK.

OEBio TK interaction predicates

Access interactions

Functor Name

with given interaction type

OEHasInteractionHintType

with given atom

OEHasInteractionHint

with given residue

OEHasResidueInteractionHint

contact

OEIsContactInteractionHint

hydrogen bond

OEIsHBondInteractionHint

inter-molecular hydrogen bond

OEIsIntermolecularHBondInteractionHint

intra-molecular hydrogen bond

OEIsIntramolecularHBondInteractionHint

chelator

OEIsChelatorInteractionHint

inter-molecular chelator

OEIsIntermolecularChelatorInteractionHint

intra-molecular chelator

OEIsIntramolecularChelatorInteractionHint

covalent

OEIsCovalentInteractionHint

clash

OEIsClashInteractionHint

salt-bridge

OEIsSaltBridgeInteractionHint

T and Pi-stacking

OEIsStackingInteractionHint

cation-Pi

OEIsCationPiInteractionHint

halogen bond

OEIsHalogenBondInteractionHint

inter-molecular

OEIsInterInteractionHint

intra-molecular

OEIsIntraInteractionHint

non-ideal hydrogen bond

OEIsNonIdealHBondInteractionHint

unpaired ligand

OEIsUnpairedLigandInteractionHint

unpaired protein

OEIsUnpairedProteinInteractionHint

The following logical operations allow to combine both the built-in and the user defined interaction predicates.

Interaction Composite Functors

Composite Functor

Description

OENotInteractionHint

logical not

OEOrInteractionHint

logical or

OEAndInteractionHint

logical and

Accessing Calculated Interaction Hint Geometries

When interaction hints are perceived using the OEPerceiveInteractionHints function, various geometries (such as distances and angles) are calculated that are checked against the geometric constraints stored in the given OEPerceiveInteractionOptions class.

The following code snippet shows how to access these calculated geometries:

oebio.OEPerceiveInteractionHints(asite);
OEHBondInteractionHint hbond = new OEHBondInteractionHint(OEHBondInteractionHintType.LigandDonates);
OEHasInteractionHintType hbondpred = new OEHasInteractionHintType(hbond);

for (OEInteractionHint inter : asite.GetInteractions(hbondpred)) {
    OEInteractionHintTypeBase itype = inter.GetInteractionType();
    System.out.println("Calculated geometries for '" + itype.GetName() + "' interaction type:");
    for (String gname : inter.GetCalculatedGeometries())
        System.out.println(gname + ":\t" +
            String.format("%.3f", inter.GetCalculatedGeometry(gname)));
}

For the OEHBondInteractionHintType.LigandDonates hydrogen bond interaction type, three geometries are calculated:

The “distance” values are always given in Angstroms and the “angle” values are always given in radians. The output of the code snippet above might look like this:

Calculated geometries for 'bio:active-site:hbond:ligand2protein' interaction type:
bio:interaction:distance       : 2.722
bio:intaraction:acceptor-angle : 0.155
bio:interaction:donor-angle    : 0.241

For different interactions, different geometries are calculated. The following snippet shows how to access the names of the geometries that are available for a given interaction type using the OEGetCalculatedInteractionGeometries function:

OEHBondInteractionHint hbondacc = new OEHBondInteractionHint(OEHBondInteractionHintType.LigandAccepts);
System.out.println("Calculated geometries for '" + hbondacc.GetName() + "' interaction type:");
for (String geom : oebio.OEGetCalculatedInteractionGeometries(hbondacc))
    System.out.println(geom);

All interaction geometry names start with the bio:interaction: prefix. However, both the OEInteractionHint.HasCalculatedGeometry and OEInteractionHint.GetCalculatedGeometry methods accept names with or without the bio:interaction: prefix.

The following code snippet shows how to access the calculated geometries directly:

if (inter.HasCalculatedGeometry("distance")) {
    double distance = inter.GetCalculatedGeometry("distance");
    System.out.println("distance: " +
                       String.format("%.3f", distance) + " Angstrom(s)");
}
if (inter.HasCalculatedGeometry("acceptor-angle")) {
    double angle = Math.toDegrees(inter.GetCalculatedGeometry("acceptor-angle"));
    System.out.println("acceptor angle: " +
                       String.format("%.3f", angle) + " degree(s)");
}

The output of the code snippet above might look like this:

distance: 2.722  Angstrom(s)
acceptor angle: 8.863 degree(s)

Hint

It is a good practice to call OEInteractionHint.HasCalculatedGeometry prior to invoking the OEInteractionHint.GetCalculatedGeometry method to check whether the interaction hint has a geometry with a given name.

Currently, the following names are used for the interaction geometries:

  • bio:interaction:distance

  • bio:interaction:angle

  • bio:interaction:acceptor-angle

  • bio:interaction:donor-angle

For most interactions (except the unpaired ones), the calculated distance is available by using the bio:interaction:distance name. None of the unpaired interactions have any calculated geometries since they only “suggest” how they could contribute to the binding but are not actually formed in the complex.

A calculated geometry, such as a distance, can have different meanings based on the interaction type. For example, in a hydrogen bond interaction it means the distance between the acceptor and donor heavy atoms. For a pi-staking interaction, it means the distance between the center of the two ring systems. The following table shows the correspondence between the calculated geometries and the geometric constraints.

Set method

Interaction type

Associated geometry name

SetMaxHBondDistance

hbond

bio:interaction:distance

SetMaxChargeAidedHBondDistance

hbond (charged)

bio:interaction:distance

SetMaxNonIdealHBondDistance

non-ideal hbond

bio:interaction:distance

SetMaxAcceptorAngle

hbond

bio:interaction:acceptor-angle

SetMaxDonorAngle

hbond

bio:interaction:donor-angle

SetMaxNonIdealAcceptorAngle

non-ideal hbond

bio:interaction:acceptor-angle

SetMaxNonIdealDonorAngle

non-ideal hbond

bio:interaction:donor-angle

SetMaxMetalBondDistance

chelator

bio:interaction:distance

SetMaxSaltBridgeDistance

salt bridge

bio:interaction:distance

SetMaxCationPiDistance

cation-Pi

bio:interaction:distance

SetMaxCationPiAngle

cation-Pi

bio:interaction:angle

SetMaxPiStackDistance

Pi-stacking

bio:interaction:distance

SetMaxPiStackAngle

Pi-stacking

bio:interaction:angle

SetMaxTStackDistance

T-stacking

bio:interaction:distance

SetMaxTStackAngle

T-stacking

bio:interaction:angle

SetMaxHalogenBondDistance

halogen bond

bio:interaction:distance

SetMaxHalogenAngle

halogen bond

bio:interaction:angle