I am facing troubles in refining structure  (C2221 space group) at 4A resolution . The current Rwork/Rfree stalls at 35.8/37.7.Given low resolution, the total number of unique reflections accounts to 19356 while number of atoms in pdb corresponds to 3893. At this very low resolution, the number of available observations are insufficient to support the refinement of four parameters (x, y Z, Biso)  and therefore i think the modeled atomic displacement (B-factors) are excessively high ranging from 100-280 which is scary at this moment. 

Is there any illustrative parameters to work on which might be useful for putting control over the shooting up of B-factors during refinement. I tried incorporating the group B-factor refinement with TLS group but seems like is not much useful. 

I would appreciate any incoming suggestions and thoughts on adopting crucial refinement strategies pertaining to this resolution. 

Thank you 

Appu