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
