Hi All:
There are two published x-ray structures (very similar, RMSD<1A if ignore
2 loops) available for a wild-type protein; let's call these two
structures M1 and M2. They belong to the same space group but with large
differences in unit cell dimensions (over 10%, or 10A in each dimension,
cross R>30%).
Now I have some (deletion) mutant structures to solve and the unit cell
dimensions of these mutant crystals are very similar to one of the crystal
forms (say M2)mentioned above. All these crystals including the wild-type
diffract to low resolution (~3.5-4A) and have no NCS, so the
parameter/data ratio must be very high.
My question is: would model bias be less if I use the structure model
that is very different (i.e M1) in unit cell dimensions? In other words,
if I only do molecular replacement and rigid body refinement, and look at
the 2Fo-Fc and Fo-Fc maps right after this, will I see a less biased map
by using M1 as the model instead of M2?
In my naive thinking, since the M1 and M2 crystal forms are so different,
and the parameters in the M1 model has essentially not been refined
against the M2 data (which the mutant belong to). Using M1 as the model
to calculate maps must be different from using M2, and presumably, with
less model bias towards the wild type structure?
In contrast, if the M2 model is used for these mutants. since all
parameters of M2 has been fully refined against similar data in wild-type,
all these parameters might presumably have been "contaminated" by the
wild-type data? i.e. all the parameters (all parts of the wt model) have
been adjusted "together" to fit the data. If I use this model on a very
similar mutant data, will it be more likely to generate back the wt
model(more biased)?
Do you think this is a valid argument?
Regards,
Weikai
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