Drug target deconvolution in Plasmodium falciparum using thermal proteomics profiling

Early identification of a compound’s mode of action can greatly benefit the discovery process. Thermal proteomics profiling (TPP) is a powerful, unbiased tool that can be used to identify potential ligands of protein targets. TPP takes advantage of the fact that a ligand binding to its target protein can significantly stabilise that protein, increasing its melting temperature (Tm). We previously optimised this technique for use in drug target deconvolution in the kinetoplastid parasite, Leishmania donovani1 and here report the optimisation and validation of TPP in the malaria-causing parasite P. falciparum.