Dear ccp4 members

I have something that surprises me with molecular replacement. I have obtained 
a 
solution for a single point mutation using Phaser, the solution seems ok. I do 
one round of refinement with refmac and I check the structure using molprobity 
before I even start really to refine it. The structure looks very good. 
MolProbity gives all green lights. Then I start to "fix" the structure, I add 
waters, I check fit to density, rotamers, geometry etc, I do some more 
refinements. I check with MolProbity and it looks a lot worse... many clashes, 
many bad ramachandran and rotamers, many red lights. I do not understand. How 
can each successive round of refinement make the structure worse and worst? Is 
there a fundamental problem, perhaps, like undiagnosed NCS or incorrect space 
group or incorrect MR solution? Could they be giving these strange result do 
you 
think? 


Thanks
Careina

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