Accelerated polypharmacology drug discovery platform


Type of Project: Theory Project

Location: Donostia

Aitor Bergara

Aritz Leonardo

Therapeutic drugs produce beneficial effects by entering into pockets within proteins. Often, those pockets are made with more than one gene product. Calmodulin (CaM) combines with more than 300 different proteins, thereby generating novel pockets that can be recognized by different drugs. For instance, Riluzole, the first treatment approved for amyotrophic lateral sclerosis (ALS), fits into a particular compartment within the interface between CaM and a potassium channel changing the way it works, whereas trifluoperazine alters the interaction between CaM and a water channel protein, reversing for the first time edema. We propose to systematically sculpt all pockets formed at the CaM/target interface with the use of computers to repurpose or find drugs that fit there because filling different pockets formed by CaM and a particular target has an enormous therapeutical potential for ALS, edema and other diseases.