Molecular docking study of macrocycles as Fk506-binding protein inhibitors

•We compare isomerase enzymes from humans and malarial parasites.•We use docking methods to compare binding affinities of various macrocycles.•Bulky groups attached to rapamycin-derivatives show improved binding in malarial parasites.•Bulky groups attached to rapamycin-derivatives show decreased binding in humans.•This distinction in binding affinities offers insight into malarial inhibition.

To prepare for future resistance, new methods are being explored for novel treatment of malaria. The current work uses high performance docking methods to model different substrates binding into the active sites of varying Homo sapien and Plasmodium peptidyl-prolyl cis/trans isomerase enzymes and compares their subsequent docking scores. This approach has shown that the substrates ILS-920 and WYE-592 will bind less-favourably with hFKBP12 and PfFKBP35 compared to a competing substrate rapamycin; however, the binding appears to be more favourable in PvFKBP35. This could suggest a possible target for inhibition of the Plasmodium vivax parasite.

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