David Koes has, I believe, already extended this limit:
https://github.com/openbabel/openbabel/pull/1546

This is now in the master, if you want to try building from the git repo.

It's a file size limit, rather than no. of molecules so using SMILES
should also help.

- Noel

On 27 April 2017 at 11:55, Chris Swain <sw...@mac.com> wrote:
> I just tried to create a fastsearch index for a large file containing
> several million structures and I get this error.
>
> *** Open Babel Error  in WriteChemObject
>   The datafile must not be larger than 4GB
>
> Is there a limit in the number of structures that can be handled? Or would
> it be better to switch from an sdf file to SMILES as the input file?
>
> Cheers,
>
> Chris
>
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