Covalent

Covalent forms of a molecule are marked within the Chem.Mol instances in fragmenstein with a “dummy atom”. This is element symbol * within RDKit and smiles, but R in a mol file and PDB file.

This is essential for the params file (topology file for the ligand).

Consequently, hits are best extracted with Victor.extract_mols or Victor.extract_mol. Fragalysis does not do this, so the hits from there will be treated as regular compounds.

Monster

A molecule with a single atom is passed to attachment argument of Monster, then the covalent linker if absent in the hits is anchored to that atom. If you know a ligand that is covalent Victor.find_attachment can be used to extract the attachment atom.

Warheads

Victor has a cysteine reactive warheads operations In the class attribute .warhead_definitions are stored conversions and atom names (cf. MProVictor for an example).

acrylamide C(=O)C=C => C(=O)CC* chloroacetamide C(=O)C[Cl] => C(=O)C* nitrile C(#N) => C(=N)* vinylsulfonamide S(=O)(=O)C=C => S(=O)(=O)CC* bromoalkyne C#C[Br] => C(=C)*

Additionally, .possible_definitions contains two (or more) that may be added experimentally (don’t currently work).

aurothiol S[Au]P(CC)(CC)CC => S[Au]* aldehyde [C:H1]=O => C(O)*

There is a quick way to get a warhead definition too

Victor.get_warhead_definition(warhead_name)

In terms of Rosetta constraints (restraints), these can be added with

Victor.add_constraint_to_warhead(name=constrain_name, constraint=constraint)

For example:

  • chloroacetamide: AtomPair  H  145A  OY  1B HARMONIC 2.1 0.2

  • nitrile: AtomPair  H  145A  NX  1B HARMONIC 2.1 0.2

  • acrylamide: AtomPair  H  143A  OZ  1B HARMONIC 2.1 0.2

  • vinylsulfonamide: AtomPair  H  143A  OZ1 1B HARMONIC 2.1 0.2

Currently, only cysteine details are known to Victor. Cf. .covalent_definitions.

To convert a react_ive_ SMILES to a dummy-atom–marked react_ed_ SMILES:

Victor.make_all_warhead_combinations(smiles, warhead_name)

Untested backdoor

The default dummy atom can be overridden with Monster.dummy:Chem.Mol and Fragmenstein.dummy_symbol:str.