By taking into account the spatial arrangement of binding sites on a target protein, high-affinity multivalent ligands that geometrically complement their target can be designed and synthesized.
Such a protein can be locked in a conformation that is a poor representation of an actual spatial arrangement of binding site amino acid residues upon ligand binding [61], making it a poor candidate for target based virtual screening studies.
A candidate for such a factor is the promoter architecture, which includes such things as the number and position of nucleosomes, the arrangement of binding sites, and the overall spacing of elements throughout the promoter.
Here, we combine DNA sequence analysis and genome-wide expression data to discern the constraints on the arrangement of binding sites for transcription factors involved in regulating the synthesis of sulfur-containing amino acids in the yeast Saccharomyces cerevisiae.
This arrangement of binding sites likely enables Norrin to form a ternary complex.
The string emitted in the match state was chosen by another probabilistic process, which models the arrangement of binding sites and non-binding ("background") sites by PWM.
Presumably, the overall 'A'-shaped RRE topology (Fang et al., 2013) and arrangement of binding sites dictates the positioning of newly recruited subunits.
Through specific structural features including high density and a particular arrangement of binding sites, multivalent ligands exhibit unique capabilities to cluster receptors.
However, the arrangement of binding sites within Drosophila enhancers is highly flexible (Ludwig and Kreitman, 1995; Ludwig et al., 1998, 2005; Hare et al., 2008), and we have struggled to find any evidence for strong 'grammatical' effects in enhancer organization.
In the NFKB1 gene a similar arrangement of binding sites along the promoter sequence can be observed, and many NF-κB-family related TFBS are found in single promoter analysis, but cross-species comparison reveals quite low conservation of promoter sequences and visible differences between human and chimpanzee as compared to mouse and cattle promoter structures.
