GOLD docking in API - ligand flexibility, water handling and more

More advanced settings are now available when docking with GOLD programmatically through the API. Here’s what has changed in the 2021.1 release.

Docking with GOLD - genetically optimised ligand docking - is well validated and trusted across academia and industry. The ability to perform docking programmatically through the API further opens this functionality for computational chemists to use GOLD docking in workflows. Previously some advanced features in GOLD were only accessible in the graphical user interface Hermes, but in this release they are now accessible in the API.

 

You can now configure a docking run fully programmatically, including: water handling, side chain flexibility, pharmacophore constraints, plus additional GOLD docking configuration flags.

 GOLD docking in CSD Python API

Which parameters can be controlled in the GOLD API?

It is now possible to specify water molecules that are important to ligand binding.

Both the toggle_state and spin_state parameters have been exposed. The former leaves the docking program to decide whether the water should be present or absent (bound or displaced by the ligand) during the docking. The spin option control the orientation of the water molecules.

You can also model protein flexibility by allowing side chains to rotate within user-defined bounds during docking. This means that up to 10 flexible side chains will be allowed to undergo torsional rotation around one or more of their acyclic bonds.

Finally, pharmacophore constraints can be used to bias the docking towards solutions in which particular regions of the binding site are occupied by specific types of ligand atom (e.g. hydrogen-bond donor, hydrogen-bond acceptor, ring centre).

Several flags to enable ligand flexibility have now been exposed to the CSD Python API, including the capability to flip ring corners. This will result in GOLD performing a limited conformational search of cyclic systems by allowing free corners of rings to flip above or below the plane of their neighbouring atoms. Alternatively, a library of ring conformations extracted from the Cambridge Structural Database (CSD) can be utilised by GOLD. This allows GOLD to vary ligand non-fused ring conformations during docking.

The full list of flags is:

  • flip_planar_nitrogen

  • flip_free_corners

  • flip_amide_bonds

  • flip_pyramidal_nitrogen

  • save_lone_pairs

  • match_template_conformations

  • rotate_carboxylic_hydroxyl_groups

  • use_torsion_angle_distributions

  • fix_ligand_rotatable_bonds

  • rotatable_bond_override_file

  • fix_all_protein_rotatable_bonds

  • solvate_all

  • use_internal_ligand_energy_offset

 

Learn more about docking with GOLD and the CSD Python API

 

Watch on demand: What's Up webinar from July 2021 where I presented more information about this feature.

For more details please see the 2020.1 GOLD User guide.

See examples of GOLD docking in use in case studies here.

Learn the basics of docking with GOLD in our YouTube playlist.

Read more about the CSD Python API here.