title: Computational insights into the suicide inhibition of Plasmodium falciparum Fk506-binding protein 35.
abstract: 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.
authors.affiliation: Department of Chemistry, Dalhousie University, 6274 Coburg Road, Halifax, Nova Scotia B3H 4R2, Canada.
authors.forename: Corey A
authors.initials: CA
authors.lastname: MacDonald
authors.affiliation: Department of Chemistry, Dalhousie University, 6274 Coburg Road, Halifax, Nova Scotia B3H 4R2, Canada. Electronic address: russell.boyd@dal.ca.
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Boyd
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology*; D003198:Computer Simulation; D015195:Drug Design; D004351:Drug Resistance / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology*; D010966:Plasmodium vivax / Q000187:drug effects / Q000201:enzymology; D011789:Quantum Theory; D013329:Structure-Activity Relationship; D022021:Tacrolimus Binding Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D000962:Antimalarials; D022021:Tacrolimus Binding Proteins; D019696:Peptidylprolyl Isomerase
keywords: FKBP35; Fk506-binding protein; Malaria; Peptidyl-prolyl cis/trans isomerase; Plasmodium falciparum; Plasmodium vivax; Quantum mechanics/molecular mechanics; Suicide inhibition