Computational insights into the suicide inhibition of Plasmodium falciparum Fk506-binding protein 35

Bioorg Med Chem Lett. 2015 Aug 15;25(16):3221-5. doi: 10.1016/j.bmcl.2015.05.079. Epub 2015 May 31.


Malaria is a parasite affecting millions of people worldwide. With the risk of malarial resistance reaching catastrophic levels, novel methods into the inhibition of this disease need to be prioritized. The exploitation of active site differences between parasitic and human peptidyl-prolyl cis/trans isomerases can be used for suicide inhibition, effectively poisoning the parasite without affecting the patient. This method of inhibition was explored using Plasmodium falciparum and Homo sapiens Fk506-binding proteins as templates for quantum mechanics/molecular mechanics calculations. Modification of the natural substrate has shown suicide inhibition is a valid approach for novel anti-malarials with little risk for parasitic resistance.

Keywords: FKBP35; Fk506-binding protein; Malaria; Peptidyl-prolyl cis/trans isomerase; Plasmodium falciparum; Plasmodium vivax; Quantum mechanics/molecular mechanics; Suicide inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimalarials / chemical synthesis*
  • Antimalarials / pharmacology*
  • Computer Simulation
  • Drug Design
  • Drug Resistance / drug effects
  • Humans
  • Models, Molecular
  • Peptidylprolyl Isomerase / antagonists & inhibitors
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / enzymology*
  • Plasmodium vivax / drug effects
  • Plasmodium vivax / enzymology
  • Quantum Theory
  • Structure-Activity Relationship
  • Tacrolimus Binding Proteins / antagonists & inhibitors*
  • Tacrolimus Binding Proteins / chemistry
  • X-Ray Diffraction


  • Antimalarials
  • Tacrolimus Binding Proteins
  • Peptidylprolyl Isomerase