Conformational variations are of particular importance in drug target modulation and molecular interaction. Functional Proteomic endeavors could therefore fulfill an urgent pharmacological need, once the regulatory and conformational variability of protein activity can be identified, isolated and measured. ProFACT's SeraFILE™ fulfills this purpose, integrating data-reporting infrasturcture already available, to produce more precisely defined functional proteomic characterizations.

This has immediate value in the discovery, early validation and assay development of biomarkers. Furthermore, as significant conformational events accompany the binding of drugs, functional proteomic profiles offer a direct link to drug development. Consider that a conventional drug development strategy is to lock in the latent (or attenuated) conformation usually through competitive binding to the substrate site; for kinases as an example, the ATP binding pocket is a common target. There are two fundamental deficiences to this strategy: 1) in many enzymes families like kinases, the active domain sites are highly conserved across multiple enzymes and so these drug candidates promiscuously interfere with normal cellular function, and 2) latent states are in much higher relative abundance than their "activated" counterparts, and so drug candidates targeting latent states must have comparatively higher dosages.

SeraFILE can compartmentalize alternate conformers, essential to understand if up-regulated enzyme pathways are due to the overall increase in enzyme abundance, its localization and microenvironments within the cell, allosteric modulation, or changes in its assembly/stability. An important outcome of functional proteomic investigations is to identify the factors that accompany (and potentially cause) higher catalysis when observed in disease samples. This provides a new drug development strategy. Rather than pairing small molecules to the attentuated conformer- the conventional drug discovery route, the ProFACT paradigm would screen small molecules that would pair and modulate alternate conformations. The advantages are that alternate conformations can be more specific to the disease phenotype, and especially when hyperactive conformers can be compartmentalized, lower stoichiometric requirements. These combined advantages would effectively translate to a higher therapeutic index.