The Open Source Malaria
(OSM) consortium is developing compounds
that kill the human malaria parasite, Plasmodium falciparum, by targeting PfATP4, an essential ion pump on
the parasite surface. The structure of PfATP4 has
not been determined. Here, we describe a public competition created
to develop a predictive model for the identification of PfATP4 inhibitors, thereby reducing project costs associated with the
synthesis of inactive compounds. Competition participants could see
all entries as they were submitted. In the final round, featuring
private sector entrants specializing in machine learning methods,
the best-performing models were used to predict novel inhibitors,
of which several were synthesized and evaluated against the parasite.
Half possessed biological activity, with one featuring a motif that
the human chemists familiar with this series would have dismissed
as “ill-advised”. Since all data and participant interactions
remain in the public domain, this research project “lives”
and may be improved by others.
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