Deciphering the Impact of Mutations on <i>Pf</i>DHPS Active Site and Sulfadoxine Binding: Structural Insights from Molecular Dynamics Simulations.

ABSTRACT: The antimalarial combination of sulfadoxine-pyrimethamine is used as a preventive treatment in pregnant women and children in Africa. Sulfadoxine inhibits the Plasmodium falciparum dihydropteroate synthase (PfDHPS), but resistance has emerged through point mutations in this enzyme. In this study, we investigate the impact of mutations on the structural and dynamic properties of PfDHPS using molecular dynamics simulations. Our results show that PfDHPS maintains overall structural integrity across various combinations of resistance-associated mutations. However, significant differences emerge in ligand binding. Sulfadoxine binding is particularly impacted and shows reduced stability in the mutant systems compared to the wild-type enzyme, while the natural substrat

SUBMITTER: Guemas E 

PROVIDER: S-EPMC12566285 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature