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Using molecular docking, molecular dynamics and analysis of conserved waters in the binding site, we identified a favourable binding mode for piperidin-4-yl and 4-cyclohexyl pyrrole-2-carboxamides while predicting unfavourable interactions with the active site for piperazine pyrrole-2-carboxamides.
So, combining surface and electron donor-acceptor profile of the selected region at ATP binding site, we identified a pharmacophore that can be potentially employed to design DDX3X specific ATP analog (Figure 4C).
For each binding site we identified all genes (knownGene table from UCSC genome browser database [ 46]), where the TSS is located +/-100 kb from the center of the binding site.
We refined this list by focusing on target genes whose expression was inversely correlated with the miRNA expression (i.e. potentially downregulated), and using a Targetscan context + score of < −0.30 for at least one binding site, we identified five predicted gene targets for miR-29b and four for miR-223 (Table 4).
All of these mechanisms are likely to be important for increasing the magnitude of the cryocooling penalty of CcP residue His96.[ 12] In contrast to the behavior of benzimidazole at the cryptic binding site, we identified two examples where the cryocooling penalty does not dominate over other contributions to binding.
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The binding sites we identified correlate quite well with those identified by another group that used ChIP-seq to uncover HSF binding sites in S2 cells [31].
These represent ~25% of all the σ binding sites we identified.
Using genome-wide analysis of MBD4 binding sites, we identified new targets potentially co-regulated by MBD4 and DNA methylation.
Despite the change in binding sites, we identified more than 25,000 reproducible Rxrα binding sites with only a small fraction of chromatin that represented 5 mg liver tissue.
Interestingly, this motif is similar to one present in the binding sites we identified for the paralogous transcriptional activator SsuR [ 15].
Of the FOXM1 binding sites we identified in TAM-treated cells, 55% were also found in the Sanders et al. study.
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