Structural Exploration of the PfBLM Helicase-ATP Binding Domain and Its Implications in the Quest for Antimalarial Therapies.

Background objectives: The battle against malaria has witnessed remarkable progress in recent years, characterized by increased funding, the development of life-saving tools, and a significant reduction in disease prevalence. Yet, the formidable challenge of drug resistance persists, threatening to undo these gains.

Methods: To tackle this issue, it is imperative to identify new effective drug candidates against the malaria parasite and exhibit minimal toxicity. This study focuses on discovering such candidates by targeting PfRecQ1, also known as PfBLM, a vital protein within the malaria parasite. PfRecQ1 plays a crucial role in the parasite's life cycle and DNA repair processes, making it an attractive drug development target. The research employs advanced computational techniques, including molecular modeling, structure-based virtual screening (SBVS), ADMET profiling, molecular docking, and dynamic simulations.

Results: The study sources ligand molecules from the extensive MCULE database and utilizes strict filters to ensure the compounds meet essential criteria. Through these techniques, the research identifies MCULE-3763806507-0-9 as a promising anti-malarial drug candidate, surpassing the binding affinity of potential antimalarial drugs. However, it is essential to underscore that the drug-like properties are primarily based on in silico experiments, and wet lab experiments are necessary to validate these candidates' therapeutic potential.

Interpretation conclusion: This study represents a critical step in addressing the challenge of drug resistance in the fight against malaria.