Dear CCP4ers, While trying to refine a protein-ligand structure (reso=2.9A) I notice that the density (2Fo-Fc)for the ligand is discontinuous. I also notice that the density for the residues in the ligand binding pocket (LBP) is also very feeble. And when I refine the ligand occupancy the density for the ligand appears and covers almost all the molecule, and the occupancy refines to <1.0.
However, I cannot refine the occupancy/B factors for the LBP residue side chains because the occupancy stays at 1.0 (and if I change it manually, it returns to 1) and the B factors (group & individual) remain close to the average for the remainder of the molecule. If I omit the LBP residue side chains, I get some Fo-Fc density suggesting that these side chains are real. Is there previous evidence for such phenomena suggesting multiple conformations/dynamics/loose binding? Is there a way to quantify the dynamics associated with the side chains (as with the ligand where the occupancy is <1.0) so I can argue it out with potential manuscript reviewers? The R-factor/R free #s (22%/19%) suggest that the refinement is nearing convergence. Best regards, Kumar.
