For two organic molecules of essentially unlimited size (up to and including, and sometimes exceeding MW = 1000 g/mol), I would like to generate all possible dimer pairs in vacuum. The pairs may be heterogeneous, so there could be one molecule of MW=1000 g/mol paired with something that is only MW=50 g/mol.

The objective is to find the lowest energy (preferably lowest free energy) dimer pair, in vacuum. The energy minimization I would count as an additional step. Given a set of dimer pairs I can take care of screening energies on my own, but if it will do it, so much the better.

This sort of thing is routinely done for crystal structure prediction, where one generates unit cells, and then crystals. Is it perhaps best to retrofit the more complex operation of crystal structure prediction in something like PyXtal.py, COMPACK, GLEE etc, as examples, to request only dimers rather than all possible crystal structures?

Bonus if the software is open source and MIT licence.

  • $\begingroup$ Maybe it is helpful if you specify your skill level. Generating the starting geometries with short python scripts would be one possibility. $\endgroup$
    – Greg
    Commented Nov 23, 2021 at 18:47

1 Answer 1


Generating all possible structures systematically might be difficult. When it comes to the generation and refinement of chemically useful structure guesses, I'd recommend looking into CREST by Stefan Grimme. It will sample your entire structure space, i.e, not only intermolecular docking motifs, but also intramolecular conformations. It uses an MM approach with some additional biasing and crossover techniques to sample the total conformational search space. Beware though that with large enough problems, it will still be difficult to judge how complete your coverage of that search space is.

  • $\begingroup$ Do you know of any examples for dimers? conformation searching for an ideal gas molecule seems trivial. I am not quite sure how to specify a dimer though? $\endgroup$
    – Wesley
    Commented Jan 19, 2022 at 13:36
  • $\begingroup$ They have a mode for sampling noncovalent complexes and aggregates (NCI mode) which looks to be exactly right $\endgroup$
    – Wesley
    Commented Jan 19, 2022 at 16:14

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