Gusnia Meilin Gholam, Riyan Alifbi Putera Irsal, Fachrur Rizal Mahendra, Maheswari Alfira Dwicesaria, Josephine Elizabeth Siregar, Arif Nur Muhammad Ansori, Rahadian Zainul
Malaria poses serious problems in countries located in tropical and subtropical regions worldwide. Plasmodium falciparum is responsible for approximately 90 % of malaria-related deaths worldwide. Therefore, alternative treatments are required to effectively reduce the number of malaria cases. Therefore, the objective of this study was to explore alternative malaria treatments by identifying compounds targeting P. falciparum plasmepsin X and characterizing the interactions under various temperatures. Molecular docking was used to evaluate interactions between polyphenolic compounds from Saussurea pulchella and plasmepsin X, followed by stability analyses using molecular dynamics (MD) simulations. Selected compounds were analyzed for biological activity, reactivity, and toxicity. RMSD (root mean square deviation), RMSF (root mean square fluctuation), Rg (radius of gyration), SASA (solvent-accessible surface area), and H-bonds were evaluated. Furthermore, MM-PBSA (molecular mechanics Poisson–Boltzmann surface area), PCA (principal component analysis), and DCCM (dynamic cross-correlation matrix) were use to evaluate effects of various temperatures. Pinoresinol 4-glucoside had a binding energy of 10.006 kcal/mol and was predicted to be nontoxic. MD simulations of pinoresinol 4-glucoside were conducted at different temperatures (298 K, 300 K, 305 K, 310 K, and 320 K) over a trajectory of 150 ns, revealing a strong binding energy using the MM-PBSA method. Our findings suggest that pinoresinol 4-glucoside is an alternative treatment for malaria and should be further evaluated at the laboratory and clinical levels. © 2024 The Authors
Department of Biochemistry, Faculty of Mathematics and Natural Sciences, Bogor Agricultural University, Dramaga Campus, Bogor, 16680, Indonesia; Bioinformatics Research Center, Indonesian Institute of Bioinformatics (INBIO Indonesia), East Java, Malang, 65145, Indonesia; Eijkman Research Center for Molecular Biology, National Research and Innovation Agency, Jalan Raya Bogor Km. 46, Cibinong, Bogor, 16911, Indonesia; Postgraduate School, Universitas Airlangga, Surabaya, 60286, Indonesia; Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, 248007, India; Virtual Research Center for Bioinformatics and Biotechnology, Surabaya, 61254, Indonesia; Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Negeri Padang, Padang, 25131, Indonesia; Center for Advanced Material Processing, Artificial Intelligence, and Biophysic Informatics (CAMPBIOTICS), Universitas Negeri Padang, Padang, 25131, Indonesia
