Browsing by Author "Ouma Russell Ben Omondi"

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    In silico drug design and characterization of selected active compounds from sapium and salvia genus as anti-cancer agents using molecular docking and molecular dynamics simulations
    (Egerton University, 2025) Ouma Russell Ben Omondi
    Extensive research projects have been performed to better understand the genetic landscape and tumour development of localized and metastatic breast cancer (BC) and prostate cancer (Pca). In this study, computational studies and in vitro analysis were conducted before in vivo analysis to provide predictive insights into potential mechanisms and mitigate risks and hazards associated with animal experiments. Through molecular dynamics, ligand binding within the binding pocket of a ligand-protein was investigated using parameters such as root mean square deviation (RMSD) and root mean-square fluctuation (RMSF), along with molecular dynamics simulations that tracked ligand-receptor interactions over a 200-nanosecond (ns) simulation trajectory. This study presents studies of a far less explored ellagic acid (EA), [20-3H] phorbol- l2, l3-dibutyrate ([3H] PDBu), and [20-3H]-l2-deoxyphorbol-13-isobutyrate ([3H] DPB) key metabolites from the genus Sapium and compares with the widely studied salvianolic acid B (Sal B) from Salvia. The molecular interactions of these compounds with the proteins were determined using molecular docking and molecular dynamics simulation. The molecular dynamics simulations revealed that salvianolic acid B exhibited binding affinities of -38.49 kJ/mol, -28.87 kJ/mol, and -33.05 kJ/mol when targeting DNA lyase, topoisomerase II alpha, and mTOR, respectively. These docking scores were comparable to those of EA, exhibiting a binding affinity of-36.40 kJ/mol, -27.20 kJ/mol, and -31.80 kJ/mol when targeting DNA lyase, topoisomerase II alpha, and mTOR, respectively. Based on this, Sal B showed greater negative binding affinity indicating kinetically stable ligand-protein interactions. The dominance of the ligand- protein interactions indicate the significance of synergies such as the electrostatic interactions, Van der Waals forces and hydrogen bonds. Sal B had docking scores of - 46.86 kJ/mol and -27.24 kJ/mol respectively when docking NUDT5 and androgen receptor (AR). The findings of the molecular dynamics simulation also showed that the interaction of Sal B- protein had a stable RMSD with an average of l.5- 2.0 Angstroms (A). These in-silico results are indicative of biologic potential of Sal B as an anticancer agent. Evaluation of the RMSD values indicated that there were structural changes with time before reaching a plateau. This indicated a fixed ligand binding site. The RMSF plot also provided infomiation regarding the flexibility of the protein residues. In the studied ligand-receptor complexes, the RMSF values fluctuation did not exceed 2 A, showing that the protein residues remained relatively rigid.