In silico screening against wild-type and mutant Plasmodium falciparum dihydrofolate reductase

Modeling studies were performed on known inhibitors of wild-type as well as quadruple mutant Plasmodium falciparum dihydrofolate reductase (DHFR). GOLD was used to dock 31 pyrimethamine derivatives into the active site of DHFR obtained from the X-ray crystal structures 1J3I.pdb and 1J3K.pdb. Predicted binding affinities from a scoring function were analyzed and evaluated in order to develop criteria for selecting compounds having a greater chance of activity versus wild-type and resistant strains of P. falciparum for future high-throughput screening experiments.