Overall, the high level of stringency and the potential to search a large library of broadly dispersed random point mutations are the two most likely reasons why we were able to identify subtle surface residues with important structural and functional properties.
As a result of these studies, we show how subtle differences in residues at a surface distant from the functional site code for a conformational switch that allows the a1 homeodomain to become active in DNA binding in association with its cofactor α2.
It is also possible that changes in membrane-embedded residues have subtle effects on the orientation and activity of surface residues that make contact with the target cell.
Subtle analyses on the residue alterations uncovered the effects of five nucleotide mutations on the functions of the RNAP and capsid proteins, which account for the host-bursting efficiency.
Upon inhibitor binding, the binding-site residues undergo subtle structural rearrangement.
Boris Beizer, a legend in the field of software testing, calls this the "pesticide paradox": "Every method you use to prevent or find bugs leaves a residue of subtler bugs against which those methods are ineffectual," he says in his book Software Testing Techniques.
However, only subtle enrichment for specific residues was found.
The logo displays both significant residues and subtle sequence patterns (Additional file 3).
Because this assay is not quantitative, these results do not rule out caspase-2 possessing subtle preferences for particular residues in this position, such as its previously reported preference for valine [ 59, 60] The caspase-2 reporter strain was also transformed with a library encoding random residues in the P4, P3 and P2 positions.
Others have suggested that the effect of C90 is so strong it prevents detection of any subtler effects other residues might have [ 28].
