How to perform lead optimization after structure based pharmacophore library search

We have performed a structure-based pharmacophore (receptor whose ligand is not reported) in which, a large number of small molecules library is screened, depending upon their FitValue the small molecules are sorted, for further analysis. Cdocking protocol is performed for the ligands, further depending upon the -CDOCKER SCORE and -CDOCKER INTERACTION the ligand library is sorted. Meanwhile, ADMET and Toxicity are also checked for the ligand library.

For the lead optimization part, what do we select for "Input Fragment Libraries", What are the small molecules library do we select for the "De novo Library Generation"  

If a receptor does not have a known inhibitor how do we perform De Novo or Lead optimization part for the same?