To discriminate between these opposite binding modes, we reasoned that the reactive-site loop of the bound inhibitor would only be exposed in the ornithodorin-like conformation to allow targeting of a second serine proteinase.
Because mutants A1, B2 and D2 contained only single or double mutations that readily displayed high-affinity [H]granisetron binding, we reasoned that these subtle changes alone are sufficient to mimic the 5-HT3R-binding site.
After careful consideration of the relative orientation of the docking motif to the ATP binding site (approximately 90°, Figure 1B), we reasoned that a flexible linker might allow for better simultaneous occupation of the docking groove and catalytic site.
Since the number of binding sites used to construct the preliminary profile of CRP binding sites was relatively small (for the reason, see the Results section), in order to minimize possible bias of binding site sampling, we conducted a one-round iteration to obtain a more representative profile of the CRP binding sites.
In the search for a link between AR, focal contact sites and cytoskeleton proteins, we reasoned that FlnA, an actin-binding protein, might be involved.
Given that these mouse monoclonal antibodies are raised against different epitopes of the MYCN protein, we reasoned that MYCN binding sites identified independently by both antibodies are more likely to be genuine.
We reasoned that MBD4 binding sites that are heavily methylated might represent additional genomic targets co-bound by DNMT1 and MBD4.
We reasoned that the binding sites would be less likely to be conserved if their occurrences were deleterious, as would be expected if the potential proto-silencers occasionally silenced adjacent genes.
In an attempt to improve the identification of true target genes and making use of true PPARγ sites that went undetected (false-negatives), we reasoned that RXR ChIP-PET monosites supported by lower confidence PPARγ binding (as defined by moPET threshold of ≥2) would also identify good PPARγ∶RXR overlap binding sites.
The P4 mutation is located on the side of the α-helix that is exposed to solvent and we reasoned that this region might be the binding site on the kinase domain for YopJ (Figure 6D).
