| Autor: |
Alharbi B; Department of Medical Laboratory Science, College of Applied Medical Sciences, University of Ha'il, Ha'il, Saudi Arabia., Alharethi SH; Department of Biological Science, College of Arts and Science, Najran University, Najran, Saudi Arabia., Al-Soud WA; Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia., Ahmed Al-Keridis L; Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia., Aljohani AA; Department of Clinical laboratory Science, College of Applied Medical Sciences-Qurayyat, Jouf University, Sakaka, Saudi Arabia., Jairajpuri DS; Department of Medical Biochemistry, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain., Alshammari N; Department of Biology, College of Science, University of Ha'il, Ha'il, Saudi Arabia., Adnan M; Department of Biology, College of Science, University of Ha'il, Ha'il, Saudi Arabia. |
| Abstrakt: |
3'-phosphoadenosine 5'-phosphosulfate synthase 1 (PAPSS1) is an enzyme that critically synthesises the biologically active form of sulfate (PAPS) for all sulfation reactions. The discovery of PAPSS1 as a possible drug target for cancer therapy, specifically in non-small cell lung cancer, has prompted us to investigate potential small-molecule inhibitors of PAPSS1. Here, a structure-based virtual screening method was used to search for phytochemicals in the IMPPAT database to find potential inhibitors of PAPSS1. The primary hits were selected based on their physicochemical, ADMET, and drug-like properties. Then, the binding affinities were calculated and analyzed the interactions to identify safer and more effective hits. The research identified two phytochemicals, Guggulsterone and Corylin, that exhibited significant affinity and specific interaction with the ATP-binding pocket of PAPSS1. Structural observations made by molecular docking were further accompanied by molecular dynamics (MD) simulations and principal component analysis (PCA) to examine the conformational changes and stability of PAPSS1 with the elucidated compounds Guggulsterone and Corylin. MD simulation results suggested that the binding of Guggulsterone and Corylin stabilizes the PAPSS1 structure, leading to fewer conformational changes. This implies that these compounds may be useful in developing PAPSS1 inhibitors for the therapeutic development against non-small cell lung cancer (NSCLC). This study highlights the potential of phytochemicals as PAPSS1 inhibitors and the utility of computational approaches in drug discovery.Communicated by Ramaswamy H. Sarma. |
