Abstract: With drug resistance becoming widespread in
Plasmodium falciparum infections, the development of the alternative
drugs is the desired strategy for prevention and cure of malaria. Three
drug targets were selected to screen promising drug molecules from
the GSK library of 13469 molecules. Using an in silico structure-based
drug designing approach, the differences in binding energies of
the substrate and inhibitor were exploited between target sites of
parasite and human to design a drug molecule against Plasmodium.
The docking studies have shown several promising molecules from
GSK library with more effective binding as compared to the already
known inhibitors for the drug targets. Though stronger interaction has
been shown by several molecules as compared to the reference, few
molecules have shown the potential as drug candidates though in
vitro studies are required to validate the results. In case of
thymidylate synthase-dihydrofolatereductase (TS-DHFR), three
compounds have shown promise for future studies as potential drugs.
Abstract: In order to find the particular interaction energy
between cylcloguanil and the amino acids surrounding the pocket of
wild type and quadruple mutant type PfDHFR enzymes, the MP2
method with basis set 6-31G(d,p) level of calculations was
performed. The obtained interaction energies found that Asp54 has
the strongest interaction energy to both wild type and mutant type of -
12.439 and -11.250 kcal/mol, respectively and three amino acids;
Asp54, Ile164 and Ile14 formed the H-bonding with cycloguanil
drug. Importantly, the mutation at Ser108Asn was the key important
of cycloguanil resistant with showing repulsive interaction energy.