The conformational flexibility of GPCRs, but also to the sensitivity of docking to small changes in the protein structure. In combination, it can be exploited to identify larger numbers of ligands by docking to more than one protein conformation. Any model of a protein structure represents only one possibility from the continuum of conformations. Thus, using differently optimized models, the set of identified ligands would have changed. Yet, the overall performance, with some models being able to recognize ligands and some not, would be similar. This fact might also be considered disheartening for approaches that aim to include receptor flexibility via docking to multiple conformations of a receptor and calculating the average rank of a molecule across all structures. Eukaryotic transcription factors are AbMole BioScience Life Science Reagents grouped into families based on their common DNA binding domains. Due to their similarity of their DNA binding domains, proteins within families have the potential to bind to similar DNA motifs and this has been shown to be the case for the ETS transcription factors where only subtle differences in binding specificity can be observed in vitro. Given that there are 28 ETS family members in mammals and that they possess a similar binding potential it is unclear how biological specificity is achieved. However, insights into this have been provided by several genome-wide ChIP-seq/ChIP-chip studies, where it is clear that although there is substantial overlap in DNA binding in vivo, individual family members preferentially bind to subsets of sites. It seems likely that binding to these ‘exclusive’ sites accounts for the specificity of action of particular ETS factors. Indeed, we recently showed that in breast epithelial MCF10A cells, ELK1 binds to DNA in vivo in two distinct manners, either overlapping with binding of another ETS protein GABPA or binding to a different set of sites to GABPA. Importantly, ELK1 was shown to control cell migration and it does so through regulating the expression of genes associated with ‘unique’ ELK1 binding sites. This study therefore confirmed the hypothesis that a specific biological effect can be elicited by the binding of a single family member, in this case ELK1, to a series of target genes that are not targeted by other family members. In addition to the specific role for ELK1 in controlling MCF10A cell migration, a large number of genes targeted by ELK1 overlap with the binding of GABPA. Similarly, in human T cell lines, GABPA binding substantially overlaps that of the other ETS proteins ETS1 and ELF1. In this overlapping binding mode, GABPA is thought to control the activities of housekeeping genes such as those encoding ribosomal proteins. However, it is not clear whether GABPA functions to control specific sets of genes in an independent manner from other ETS proteins and hence drive distinct biological processes. Such a specific function appears likely, as GABPA has previously been associated with controlling many different processes. For example, it was recently demonstrated to play an important role in haematopoietic stem cell maintenance and differentiation. It also has a role as a controller of cell cycle progression and is important for the formation of a functional postsynaptic apparatus in neurons. These studies suggest that GABPA likely binds in a ‘unique’ manner to sets of genes controlling these processes. In this study we investigated the functional role of GABPA in MCF10A cells. As our previous results showed that ELK1 controls breast epithelial cell migration and this happens through regulating a set of target genes that are apparently ‘unique’ to ELK1 and not also bound by GABPA, we therefore assumed that GABPA would not affect cell migration and instead would control different biological processes.