Journal of Proteomics & Bioinformatics
Open Access
ISSN: 0974-276X
+44 1223 790975
ISSN: 0974-276X
+44 1223 790975
Abdul Rauf Shakoori
School of Biological Sciences,
Quaid-i-Azam Campus, Lahore
Pakistan
Research Article
In silico Analysis of 2, 4-Substituted Heterocycles and Glutamic Acid
Containing Antifolates as Inhibitors of Malarial (Plasmodium falciparum)
Protein, Dihydrofolate Reductase-Thymidylate Synthase
Author(s): Jawaria Munir, Zeeshan Iqbal, Daniel C Hoesli, Abdul Rauf Shakoori and Nasir UddinJawaria Munir, Zeeshan Iqbal, Daniel C Hoesli, Abdul Rauf Shakoori and Nasir Uddin
Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) function is effectively inhibited by antifolates. The binding affinity of antifolates to PfDHFR-TS is reduced due to mutations in its active site. In the present study, 33 analogues of Methotrexate (MTX), Trimetrexate (TMX), Raltitrexed (RTX) and Pemetrexed (PTX) were designed and evaluated for interaction with PfDHFR-TS by in silico methods. Analyses of drug candidates were performed by generating their docking complexes with quadruple mutant crystal structure of PfDHFR-TS using Molecular Operating Environment (MOE). Initially eight top scoring complexes and then finally two (MTX04 and PTX03) were found suitable for further optimization based on interaction pattern with active site amino acids. Analyses of structural characteristics, binding energy calculations and interaction patterns of MTX04 and PTX03 w.. View More»
DOI:
10.4172/jpb.1000341