3.5 Binding Energies

Binding energies and other binding related properties can be calculated using the OEBind class. The OEBind class serves two primary purposes: 1) to have an class in place for users to easily calculate binding related data, and 2) to show how binding related data may be calculated. OEBind is not particularly well-suited for extrememly efficient calculations required by simulations. This is because some of the data available from OEBind may be considered uninteresting for the project and there is no need to spend time calculating it, or because OEBind calculates the unbound protein and ligand properties everytime, which is unnecessary if the same protein and ligand appear in multiple calculations. The API section for OEBind is detailed with regard to implementation, so the user can see how to create their own class or set of function calls if needed.

There are two classes that store the results of a binding calculation, OEBindResults and OESimpleBindResults. OEBindResults is a superset of OESimpleBindResults. The following table contains the properties that can be acquired from OESimpleBindResults (and thus OEBindResults as well).

Property Name	Type	Get Method
Binding Energy	float	GetBindingEnergy
Bound Ligand Area	float	GetBoundLigandArea
Bound Ligand Area Energy	float	GetBoundLigandAreaEnergy
Bound Ligand Zap Energy	float	GetBoundLigandZapEnergy
Bound Protein Area	float	GetBoundProteinArea
Bound Protein Area Energy	float	GetBoundProteinAreaEnergy
Bound Protein Zap Energy	float	GetBoundProteinZapEnergy
Buried Area	float	GetBuriedArea
Buried Area Energy	float	GetBuriedAreaEnergy
Complex Area	float	GetComplexArea
Complex Area Energy	float	GetComplexAreaEnergy
Complex Zap Energy	float	GetComplexZapEnergy
Conf	OEChem::OEConfBase	GetConf
Unbound Ligand Area	float	GetUnboundLigandArea
Unbound Ligand Area Energy	float	GetUnboundLigandAreaEnergy
Unbound Ligand Zap Energy	float	GetUnboundLigandZapEnergy
Unbound Protein Area	float	GetUnboundProteinArea
Unbound Protein Area Energy	float	GetUnboundProteinAreaEnergy
Unbound Protein Zap Energy	float	GetUnboundProteinZapEnergy
Zap Energy	float	GetZapEnergy

A SimpleBind calculation with an OESimpleBindResults instance does three ZAP electrostatics calculations, one each for the protein, ligand, and complex, as well as an area analysis. A Bind calculation with an OEBindResults instance does three addition ZAP electrostatics calculations with the external dielectric constant set to the internal dielectric constant, one each for the protein, ligand, and complex. These addition calculations allow for the following properites to be acquired from OEBindResults.

Property Name	Type	Get Method
Analytic Coulombic Binding Energy	float	GetAnalyticBindingEnergy
Bound Ligand Coulomb Energy	float	GetBoundLigandCoulombEnergy
Bound Protein Coulomb Energy	float	GetBoundProteinCoulombEnergy
Complex Coulomb Energy	float	GetComplexCoulombEnergy
Coulomb Energy	float	GetCoulombEnergy
Desolvation Energy	float	GetDesolvationEnergy
Ligand Desolvation Energy	float	GetLigandDesolvationEnergy
Protein Desolvation Energy	float	GetProteinDesolvationEnergy
Unbound Ligand Coulomb Energy	float	GetUnboundLigandCoulombEnergy
Unbound Protein Coulomb Energy	float	GetUnboundProteinCoulombEnergy

For an in-depth understanding of what is calculated, the electrostatics portion of the algorithm for the SimpleBind function is shown in the API section.

A sample program for using the OEBind class is provided in the distribution and shown below.

 1 #!/usr/bin/env python
 2 #############################################################################
 3 #  Copyright (C) 2006, 2007, 2008 OpenEye Scientific Software, Inc.
 4 #############################################################################
 5 ### bind.py
 6 #############################################################################
 7
 8 import os, sys
 9 from openeye.oechem import *
10 from openeye.oezap import *
11
12 def main(argv = [__name__]):
13     if len(argv) != 3:
14         OEThrow.Usage("%s <protein> <ligands>" % argv[0])
15
16     protein = OEMol()
17
18     ifs = oemolistream()
19     if not ifs.open(argv[1]):
20         OEThrow.Fatal("Unable to open %s for reading" % argv[1])
21     OEReadMolecule(ifs, protein)
22
23     OEAssignBondiVdWRadii(protein)
24     OEMMFFAtomTypes(protein)
25     OEMMFF94PartialCharges(protein)
26     print >>sys.stderr, "protein:   " + protein.GetTitle()
27
28     epsin = 1.0;
29     bind = OEBind()
30     bind.GetZap().SetInnerDielectric(epsin);
31     bind.SetProtein(protein)
32     results = OEBindResults()
33
34     if not ifs.open(argv[2]):
35         OEThrow.Fatal("Unable to open %s for reading" % argv[2])
36     ifs.SetConfTest(OEIsomericConfTest())
37
38     ligand = OEMol()
39     while OEReadMolecule(ifs, ligand):
40         OEAssignBondiVdWRadii(ligand)
41         OEMMFFAtomTypes(ligand)
42         OEMMFF94PartialCharges(ligand)
43         print >>sys.stderr, "ligand:  %s has %d conformers" % \
44               (ligand.GetTitle(), ligand.NumConfs())
45
46         for conf in ligand.GetConfs():
47             bind.Bind(conf, results)
48             print >>sys.stderr,  " conf# %d   be = %f" % \
49                   (conf.GetIdx(), results.GetBindingEnergy())
50     return 0
51
52 if __name__ == "__main__":
53     sys.exit(main(sys.argv))

Listing:3.8 ZAP Bind Example

				ZAP Electrostatics at OpenEye Python Programming Manual

				ZAP Electrostatics at OpenEye Python Programming Manual