Checks

Example failure modes

In molecular conformation generation, docking, and de-novo molecular generation the generated molecules conformation should have a reasonable geometry including standard bond lengths and angles and no steric clash.

Bond lengths

Bond lengths fail

Bottom left carbon-oxygen bond too short

Bond lengths true

Bond angles

Bond angles fail

Bond angles off and atoms clashing

Bond angles true

Steric clash

Internal clash fail

Molecule intertwined and atoms clashing

Internal clash true

High energy conformation

Energy ratio fail

Twisted rings energetically unfavorable

Energy ratio true

Aromatic rings not flat

Flat aromatics fail

Conjugated pi bond systems should be flat

Flat aromatics true

In docking the molecular identity should be preserved including stereochemistry.

Tetrahedral stereochemistry changed

Tetrahedral stereochemistry fail

Top right oxygen facing the wrong way

Tetrahedral stereochemistry true

Double bond stereochemistry changed

Double bond stereochemistry fail

Right most double bond should be cis

Double bond stereochemistry true

In de-novo molecular generator or docking the generated molecule should be placed with in a receptor’s binding pocket without any steric clash.

Volume overlap

Volume overlap fail

Ligand and receptor clash

Volume overlap true

In addition to these geometric considerations, molecules should always pass RDKit’s chemical sanitisation checks, as well as be interconvertible with InChI strings.

More details on tests and docking method comparison

For more detailed information about the tests and for a study using PoseBusters to compare docking methods, refer to our preprint or paper:

@article{buttenschoen2024posebusters,
   title = {{{PoseBusters}}: {{AI-based}} Docking Methods Fail to Generate Physically Valid Poses or Generalise to Novel Sequences},
   shorttitle = {{{PoseBusters}}},
   author = {Buttenschoen, Martin and Morris, Garrett M. and Deane, Charlotte M.},
   year = "2024",
   journal = "Chemical Science",
   volume = "15",
   issue = "9",
   pages = "3130-3139",
   publisher = "The Royal Society of Chemistry",
   doi = "10.1039/D3SC04185A",
   url = "http://dx.doi.org/10.1039/D3SC04185A",
}