Well, the script controls the isotope effects (item ordering, filtering based on pagination etc..), so basically yes, but I cannot guarantee it will work without it correctly.
The plugin uses a separate search process, but it might be possible to change it to a very similar configuration to get almost the same results at the default search:
1. The WordPress core search only returns posts and pages, so make sure that on the General Options -> Sources panel no other post types are selected: http://i.imgur.com/C3ZBClU.png
2. The rest of that same panel should be configured as this: http://i.imgur.com/kvD0vbD.png
3. The keyword logic and the exact matching should be the default, like so: http://i.imgur.com/5ebJQwS.png
4. The ordering should be set to ‘Date descending’ and ‘Title descending’ on the General Options -> Ordering panel: http://i.imgur.com/SJ25OEd.png
5. And finally, the relevance must be turned off on the Relevance Options -> Regular engine panel: http://i.imgur.com/y0baPsT.png
If nothing else was changed, no other sources were selected, then this should give more similar results to the default wordpress search.