I have a data set of a protein in complex with an inhibitor. It a new crystal form. we have solved the same complex before as a different crystal form. But this time I am having problems with high rfree(46%) after molecular replacement. The Rmerge for the data set is 10.1% and Mattews suggests two molecules in the asu. The space group is predicted as P222. I have tried all the other seven alternative space groups but the rfree doesnt go down even after refmac refinement.

Do anybody have any idea as to how this can be solved.