Molecular docking study of macrocycles as Fk506-binding protein inhibitors

J Mol Graph Model. 2015 Jun;59:117-22. doi: 10.1016/j.jmgm.2015.04.009. Epub 2015 Apr 29.


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.

Keywords: FKBP12; FKBP35; Fk506-binding protein; Malaria; Molecular docking; Peptidyl-prolyl cis/trans isomerases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimalarials / chemistry
  • Antimalarials / pharmacology
  • Catalytic Domain
  • Humans
  • Macrocyclic Compounds / chemistry*
  • Macrocyclic Compounds / pharmacology*
  • Molecular Docking Simulation / methods
  • Peptidylprolyl Isomerase / metabolism
  • Plasmodium vivax / drug effects
  • Protein Binding
  • Protozoan Proteins / metabolism
  • Sirolimus / chemistry
  • Sirolimus / pharmacology
  • Tacrolimus Binding Proteins / antagonists & inhibitors*


  • Antimalarials
  • Macrocyclic Compounds
  • Protozoan Proteins
  • Tacrolimus Binding Proteins
  • Peptidylprolyl Isomerase
  • Sirolimus