In Silico Comparison of Anti Seizure Medications: Molecular Docking and Interaction Profile on Selected Epilepsy Targets
Faculty Mentor
Robin Elliott
Major/Area of Research
Computational Biology, Pharmacology
Description
INTRODUCTION: Epilepsy is a neurological disorder characterized by recurrent seizures caused by abnormal brain activity. Many antiepileptic drugs target enzymes and neurotransmitter systems involved in neuronal signaling. Carbonic anhydrase II regulates brain pH, while GABA-transaminase (GABA-T) breaks down the inhibitory neurotransmitter GABA. Inhibiting these targets can reduce neuronal excitability and seizure activity.
METHOD: This study used in silico molecular docking to evaluate the binding affinity of antiepileptic drugs to carbonic anhydrase II and GABA-T. Protein structures were obtained from the Protein Data Bank, and ligand structures were sourced from PubChem. Docking simulations were performed using CB-Dock2 with blind docking to identify binding pockets. Ten drugs were analyzed, including eight commonly used medications and two newer drugs, cenobamate and cannabidiol.
RESULTS: Binding affinity varied across the drugs, with more negative values indicating stronger interactions. Carbamazepine and cenobamate showed the strongest binding to carbonic anhydrase II, while oxcarbazepine and clobazam showed the strongest binding to GABA-T.
DISCUSSION/CONCLUSION: These results suggest that both commonly used and newer antiepileptic drugs differ in their interactions with target proteins, which may influence their effectiveness. This study supports the use of molecular docking as a tool for analyzing drug-target interactions. Future research should validate these findings through laboratory experiments and explore additional drug-target combinations.
In Silico Comparison of Anti Seizure Medications: Molecular Docking and Interaction Profile on Selected Epilepsy Targets
INTRODUCTION: Epilepsy is a neurological disorder characterized by recurrent seizures caused by abnormal brain activity. Many antiepileptic drugs target enzymes and neurotransmitter systems involved in neuronal signaling. Carbonic anhydrase II regulates brain pH, while GABA-transaminase (GABA-T) breaks down the inhibitory neurotransmitter GABA. Inhibiting these targets can reduce neuronal excitability and seizure activity.
METHOD: This study used in silico molecular docking to evaluate the binding affinity of antiepileptic drugs to carbonic anhydrase II and GABA-T. Protein structures were obtained from the Protein Data Bank, and ligand structures were sourced from PubChem. Docking simulations were performed using CB-Dock2 with blind docking to identify binding pockets. Ten drugs were analyzed, including eight commonly used medications and two newer drugs, cenobamate and cannabidiol.
RESULTS: Binding affinity varied across the drugs, with more negative values indicating stronger interactions. Carbamazepine and cenobamate showed the strongest binding to carbonic anhydrase II, while oxcarbazepine and clobazam showed the strongest binding to GABA-T.
DISCUSSION/CONCLUSION: These results suggest that both commonly used and newer antiepileptic drugs differ in their interactions with target proteins, which may influence their effectiveness. This study supports the use of molecular docking as a tool for analyzing drug-target interactions. Future research should validate these findings through laboratory experiments and explore additional drug-target combinations.