Bioinformatics-based profiling of essential uncharacterized Plasmodium falciparum proteins reveals novel antimalarial drug and vaccine targets

We applied an integrated computational pipeline to characterize 24 essential uncharacterized P. falciparum proteins. Analyses included physicochemical profiling, secondary and tertiary structure prediction, conserved domain and fold identification, post-translational modification mapping, subcellular localization prediction, enzyme classification, and in silico assessment of druggability and vaccine candidacy. The proteins exhibited strong enrichment in hydrophilic residues, particularly asparagine and lysine, and uniformly negative GRAVY scores, consistent with low-complexity, hydrophilic proteins. Despite this, they displayed broad chemical diversity and adopted defined structural folds, including Belta-grasp and helical bundle motifs, among others. Half of the proteins were predicted to possess enzymatic activity spanning hydrolase, transferase, oxidoreductase, and lyase classes. Six proteins emerged as high-confidence drug targets, with Pf3D7_1106500, satisfying the criteria for both drug and vaccine candidacy. This study converts a set of essential but uncharacterized parasite proteins into a prioritized panel of potential therapeutic targets, providing a rational framework for experimental validation and future antimalarial intervention development.