THE CHALLENGE
G Protein-Coupled Receptors (GPCRs) represent the largest class of membrane proteins in humans and bind almost all of the known neurotransmitters and hormones that are released synaptically or secreted into the circulatory system. GPCRs are expressed in all tissue types and organs and are associated with many diseases.
The GPCR super-family includes around 400 medically relevant targets. To date more than 110 receptors have been exploited as drug targets, while most of the remaining are orphan (130) or under-characterized.
Ion channels are complex, pore-forming membrane proteins that modulate the flow of ions across the cell membrane and control, among other functions, the resting membrane potential and all electrical signaling of the cell.
The ion channel super-family includes around 280 medically relevant targets, including many important CNS targets. Of these, less than 20% have been exploited as drug targets. Traditional drug discovery approaches for ion channel-targeting drugs, such as high throughput screening, are not possible due to challenges related to expression of wild type proteins.
GPCRs, ion channels, and other membrane proteins are difficult to work with due to their hydrophobicity and flexible nature. Increasing stability/melting temperature has been shown to lead to increased homogeneity, better crystallizability, improved antigenicity and immunogenicity.
OUR SOLUTION
Abilita Bio has developed an approach, which allows for fast and efficient identification of mutation sets that impart substantial improvements over wild type membrane proteins. Our readout method is orders of magnitude faster than existing technologies, and allows for screening of multiple mutations at once (mutation sets), which can also uncover cooperative mutations. Additionally, our technology is applicable to Orphan Receptors, since we are able to create stabilized membrane proteins in apo form (unbound).
