Adding hydrogens to protein changes the value of the strict property for h-bond interactions

[Tim Dudgeon]

I'm finding that h-bond interactions can differ depending on whether hydrogens have been added to the protein. On digging into this I find that the same interactions are found but the 'strict' property can be different.

Example code:

from oddt import toolkit, interactions

pfile = '/home/timbo/github/im/docking-validation/targets/mpro/expts/virtual-screening/work/Mpro-x1093_0/receptor_apo-desolv.pdb'
lfile = '/home/timbo/github/im/docking-validation/datasets/XChem/MPRO/Mpro-x1093_0/Mpro-x1093_0.mol'

print('Using protein:', pfile)
print('Using ligand:', lfile)

protein = next(toolkit.readfile('pdb', pfile))
protein.protein = True

print('Original (no Hs)')
ligands = toolkit.readfile('sdf', lfile)
for mol in ligands:
protein_atoms, ligand_atoms, strict = interactions.hbonds(protein, mol)
for p, l, s in zip(protein_atoms, ligand_atoms, strict):
print(p['coords'], l['coords'], s)

protein.addh()

print('Hs added')
ligands = toolkit.readfile('sdf', lfile)
for mol in ligands:
protein_atoms, ligand_atoms, strict = interactions.hbonds(protein, mol)
for p, l, s in zip(protein_atoms, ligand_atoms, strict):
print(p['coords'], l['coords'], s)

protein.removeh()

print('Hs removed')
ligands = toolkit.readfile('sdf', lfile)
for mol in ligands:
protein_atoms, ligand_atoms, strict = interactions.hbonds(protein, mol)
for p, l, s in zip(protein_atoms, ligand_atoms, strict):
print(p['coords'], l['coords'], s)

The corresponding output is:

Original (no Hs)

[ 2.714  1.994 15.977] [ 4.601  1.537 18.494] True

[ 3.132 -1.458 17.76 ] [ 4.601  1.537 18.494] False

[ 9.532  2.713 18.513] [ 8.937  1.388 21.144] True

Hs added

[ 2.714  1.994 15.977] [ 4.601  1.537 18.494] True

[ 3.132 -1.458 17.76 ] [ 4.601  1.537 18.494] False

[ 9.532  2.713 18.513] [ 8.937  1.388 21.144] False

Hs removed

[ 2.714  1.994 15.977] [ 4.601  1.537 18.494] True

[ 3.132 -1.458 17.76 ] [ 4.601  1.537 18.494] False

[ 9.532  2.713 18.513] [ 8.937  1.388 21.144] True

I can provide the inputs if needed (seems like I can add attachments here).

Any thoughts on this would be welcome.

Tim

[Maciek Wójcikowski]

Hi Tim,

I'm glad to see you on the list using ODDT.

Please check if the problem persists on the latest git master. We had an error where what you see could surface. Basically the allowed angle was wrongly calculated and the strict flag could be wrong.

----
Pozdrawiam,  |  Best regards,
Maciek Wójcikowski
mac...@wojcikowski.pl

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[Tim Dudgeon]

Hi Maciek,

Yes, using the latest doesn't show that problem

Thanks!

Tim