مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Molecular Docking Study of Cinnamaldehyde and Glutamine as Cinnamon Metabolites: Evaluating Thrombin Inhibition Potential and Therapeutic Applications in Coagulation Disorders
Molecular Docking Study of Cinnamaldehyde and Glutamine as Cinnamon Metabolites: Evaluating Thrombin Inhibition Potential and Therapeutic Applications in Coagulation Disorders
sara farahbakhsh,1,*Zarrin Minuchehr,2Mohaddeseh Salehiyan,3
1. Ph.D. Graduate in Biotechnology, Bu-Ali Sina University, Hamadan, Iran 2. PhD, Head of Department of National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran 3. Ministry of Education, Tehran, Iran
Introduction: Cinnamon (Cinnamomum verum) contains bioactive compounds like cinnamaldehyde and tannins, known for their anti-inflammatory, antioxidant, and anticoagulant properties. This study investigates the molecular interactions of cinnamaldehyde and glutamine with thrombin, a key enzyme in blood coagulation, using molecular docking simulations. Preliminary evidence suggests these metabolites may modulate thrombin activity, potentially offering therapeutic benefits for coagulation disorders. By analyzing binding affinities and inhibitory effects, the research aims to elucidate their mechanisms and compare their efficacy with existing treatments. The findings could pave the way for natural alternatives to manage thrombosis and bleeding disorders, emphasizing cinnamon’s pharmacological potential.
Methods: he molecular docking study was conducted to investigate the interactions of thrombin (PDB:1DWD) with cinnamaldehyde and glutamine, key metabolites of cinnamon. Thrombin’s 3D structure was retrieved from the RCSB PDB database, while ligand structures (cinnamaldehyde: CID 637511, glutamine: CID 5961) were obtained from PubChem in SDF format and converted to PDB using PyMol. Pre-docking preparations included removing water molecules, cofactors, and adding polar hydrogens to the protein structure in Molegro Virtual Docker. Active site cavities were identified, and a search box (radius: 20 Å; center: X=13.61, Y=-2.13, Z=24.27) was defined. Docking simulations were performed using the MolDock SE algorithm with 10 runs per ligand. Binding poses, affinity scores, and interaction patterns (e.g., hydrogen bonds, hydrophobic contacts) were analyzed to compare the inhibitory potential of both ligands. All parameters were set to default unless specified.
Results: Molecular docking analysis revealed distinct binding interactions between thrombin and cinnamon metabolites. Cinnamaldehyde exhibited strong binding affinity to thrombin's active site, with interaction energies ranging from -115.347 to -119.103 kcal/mol across four poses. Pose 4 showed the highest stability (HBond: -1.15659 kcal/mol), indicating effective hydrogen bonding with key residues (e.g., His57, Ser195). In contrast, glutamine preferentially bound to an allosteric site (energies: -208.865 to -227.747 kcal/mol), suggesting a non-competitive inhibition mechanism. Cavity analysis identified the primary binding site (163.84 ų volume) as the optimal region for cinnamaldehyde docking. Energy plots confirmed progressive stabilization of both ligands, with cinnamaldehyde demonstrating superior inhibitory potential via active-site occlusion. These results highlight cinnamon metabolites as promising modulators of thrombin activity.
Conclusion: This study demonstrates cinnamaldehyde's strong binding to thrombin's active site (interaction energies: -115 to -119 kcal/mol), suggesting its potential as an anticoagulant agent through competitive inhibition. In contrast, glutamine exhibited allosteric modulation (-208 to -227 kcal/mol), indicating a distinct regulatory mechanism. The favorable energy profiles and minimal steric clashes align with findings by Chen (2020) and Li et al. (2020), highlighting these metabolites as promising candidates for drug development. While cinnamaldehyde may directly inhibit thrombin, glutamine's allosteric effects could fine-tune coagulation. Further experimental validation is needed to translate these in silico findings into therapeutic applications for bleeding disorders.