Pf Phosphatidylserine decarboxylase: Molecular modeling and inhibithors prediction

Mamadou Sangare; Cheickna Cisse; Phillip Cruz; Oudou Diabate; Jeffrey G Shaffer; Jian Li; Seydou Doumbia; Mamadou WELE

doi:10.37591/rrjocb.v12i2.3318

Abstract

Plasmodium falciparum (P.f) is a protozoan parasite responsible for the most severe and deadly form of malaria. The resistance of Pf to last resort antimalarial drugs has been reported, there is an urgent need to identify new therapeutic candidates for drug development. Advancements in bioinformatics technologies provide potential cost and time-effective solutions for predicting therapeutic candidates. Phosphatidylserine decarboxylase (PSD) is a member of the lyase family (more specifically, the carboxy-lyases), which cut carbon-to-carbon bonds. PSD catalyzes the decarboxylation of phosphatidylserine to generate phosphatidylethanolamine, which is a critical step in phospholipid metabolism in prokaryotes and eukaryotes. The model of PSD has not been previously characterized, but it is recognized as a structural pathway for the design of new potential inhibitors for developing future antimalarial drugs. Here we investigate and propose PSD as a promising new target for Pf and build his model to identify new potential inhibitors of this new therapeutic target. PSD was extracted from the Tropical Disease Research (TDR) Targets database, which facilitates the identification and prioritization of drugs and drug targets of neglected pathogens. The 3D structure of the target protein was predicted using the AlphaFold2 server and the ligands were extracted from the Zinc Database Chemical Library. Molecular docking was performed using Autodock-Vina. Ten PSD inhibitors were identified according to affinity docking score, which ranged from -8.5 to -8.3 kcal/mol and were consistent with the Lipinski rule of five. This study provides a promising building block for experimental studies in establishing novel antimalarial drugs.