Investigation and drug design for novel molecules from natural products as inhibitors for controlling multiple myeloma disease using in-silico tools

• Published in: Journal of biomolecular structure & dynamics Vol. 43; no. 5; pp. 2463 - 2478
• Main Authors: Zari, Ali, Kurdi, Lina A. F., Jaber, Fatima A., Alghamdi, Khalid M. S., Zari, Talal A., Bahieldin, Ahmed, Hakeem, Khalid Rehman, Alnahdi, Hanan S., Edris, Sherif, Ashraf, Ghulam Md
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 24.03.2025
• Subjects: Anticancer; Binding Sites; Biological Products - chemistry; Biological Products - pharmacology; Biological Products - therapeutic use; Computer Simulation; docking analysis; Drug Design; Humans; Hydrogen Bonding; in silico analysis; misregulation; Molecular Docking Simulation; molecular dynamic simulation; Molecular Dynamics Simulation; Multiple Myeloma - drug therapy; Protein Binding; Thermodynamics; in silico analysis; misregulation; Anticancer; molecular dynamic simulation; docking analysis
• DOI: 10.1080/07391102.2023.2300409
• ISSN: 0739-1102; 1538-0254

Multiple myeloma (MM) is a disease that causes plasma cell growth in the bone marrow and immune globulin buildup in blood and urine. Despite recent advances in MM therapy, many still die due to its high mortality rate. A study using computational simulations analyzed 100 natural ingredients from the SANC database to determine if they inhibited the IgH domain, a known cause of multiple myeloma. Natural component Diospyrin inhibited the IgH enzyme with the best binding energy of −10.3 kcal/mol and three carbon-hydrogen bonds, followed by Parviflorone F complex with a binding energy of −10.1 kcal/mol and two conventional-hydrogen bonds. As a result, the Molecular Dynamic simulation was used to test the stability of the two complexes. During the simulation, the Diospyrin molecule dissociated from the protein at roughly 67.5 ns, whereas the Parviflorone F molecule stayed attached to the protein throughout. The latter was the subject of the investigation. The analysis of the production run data revealed that the Parviflorone F molecule exhibits a variety of conformations within the binding pocket while keeping a relatively constant distance from the protein's center of mass. The analysis of the production run data revealed that the Parviflorone F molecule exhibited a variety of conformations within the binding pocket while keeping a relatively constant distance from the protein's center of mass. The root mean square deviation (RMSD) plots for both the protein and complex showed a stable and steady average value of 4.4 Å for the first 82 nanoseconds of manufacture. As a result, the average value increased to 8.3 Å. Furthermore, the components of the binding free energy, as computed by MM-GBSA, revealed that the mean binding energy of the Parviflorone F molecule was −23.88 kcal/mol. Finally, after analyzing all of the examination data, Parviflorone F was identified as a powerful inhibitor of the IgH domain and hence of the MM disease, which requires further in-vivo conformation.