Of the successful designs, many feature pre-organized sites that are poised to perform their intended function, and improvements often result from disfavoring alternative functionally suboptimal states.
Further investigation of the loop contributions, via functional analysis, structural determination, and simulations, revealed differential contributions from individual loop residues and further suggested contributions both from disfavoring alternative, noncatalytic conformations and from limiting the mobility of the general base.
We disfavor the alternative possibility of end effects, as unstructured or poorly-defined nucleotides exist at both the 5' (one) and 3' (three) ends of the DNA, and we now mention this in the revised manuscript (subheading "Overall structure of the Dna2-ssDNA complex").
The latest duplication is, however, only a substantiated hypothesis; an alternative explanation, disfavored by the majority of evidence, is that the duplication is an artifact of incorrect genome assembly.
However, the apparent absence of trans-AT PKSs disfavors this alternative scenario.
Meanwhile, DNA sequences of alternative polyA sites are more disfavored by nucleosomes than constitutive sites.
The alternative, "flipped" orientation is highly disfavored in wild-type OYE 2.6 because the methoxy moiety is too large to fit in the pocket partially defined by Tyr78 and Ile113.
Presumably, the linear molecule KYG-2371, must bind streptavidin in a conformation that is disfavored by macrocyclization, though we cannot rule out the alternative possibility that a free N-terminus is involved in the binding event.
The alternative conformations 6 b and 7 b appear to be disfavored because of steric interactions between the side wall of the cyclopentadienyl ligand with the metallated arene of 6 b or the phenyl substituent of 7 b (Scheme 6 b).
This disfavored the neighbor marker method in our study, although the ranking of the alternatives is the same as in Calus et al. [ 22].
