A Promising Discovery for Schizophrenia and Parkinson's Disease

Assoc. Prof. Dr. Serdar Durdağı, faculty member at the Department of Biophysics of Bahçeşehir University, has achieved a first for patients with Parkinson's disease and schizophrenia.

"IT WILL LEAD THE WAY IN THE TREATMENT OF SCHIZOPHRENIA AND PARKINSON'S DISEASE"

It all actually began with a coincidence. Working on computer-aided drug design, Dr. Durdağı developed a model to reveal the crystal structure of the Dopamine-2 receptor and published it in a journal. Prof. Dr. Philip Seeman of the University of Toronto, who discovered the Dopamine-2 receptor in 1975 and has long pursued hope for Parkinson's and schizophrenia patients, contacted Dr. Durdağı, said he was also working in this direction and expressed his wish to collaborate. Accepting with great pride, Durdağı further advanced the model he had been working on for three years together with Prof. Seeman. With the model, whose three-dimensional structure was revealed using computer-aided methods, the fight against diseases such as schizophrenia and Parkinson's has entered a new era. "He liked the model very much and said it matched his own values. I was very proud of this. Until then we had only developed the monomer forms of the Dopamine-2 receptor. Together with the professor, we also developed its dimer forms. Through this joint study, we made a valuable contribution to the literature."

"WE REVEALED THE STRUCTURE OF DOPAMINE THROUGH SIMULATIONS"

Stating that they had been carrying out the project since 2012 and had worked on it intensively for the past four to five years, Durdağı said: "Last year we developed and published this model, and one day after publication, Prof. Philip Seeman of the University of Toronto, who discovered the Dopamine-2 receptor, sent me an e-mail asking for my model. I shared it with him and he said the model was highly consistent with experimental structures. He said he wanted to test his own experimental data on our model. I gladly accepted and we started working together. He told me he had two molecules, dopamine and apomorphine, whose binding affinities differed from each other. We tested these two molecules in our model, and the results matched the experimental findings exactly. In this study, we revealed the three-dimensional structure of the Dopamine-2 receptor with the help of homology modeling and energy simulations based on experimental data."

“"IT WILL BE USED TO DEVELOP NEW DRUGS WITH REDUCED SIDE EFFECTS"

"Once we reveal the drug mechanism, neurodegenerative diseases (disorders of the nervous system) such as Parkinson's and schizophrenia will be much better understood," said Durdağı. "We believe the model we developed will play a leading role in discovering more effective molecules with reduced side effects. Our aim is to use these structural models to examine drug-receptor interactions at the atomic level and, by elucidating the molecular mechanisms, to develop next-generation drugs with reduced side effects. I believe our study can pave the way for new forms of treatment and new drugs. Certain drugs are used to manage these diseases, but their development currently faces major challenges. The main reason has been that the crystal structure of Dopamine-2, a particularly important receptor, was not known. For a molecule without a crystal structure, there is only one way left: revealing its three-dimensional structure with what we call molecular modeling methods, and this is exactly what we achieved. The more models are developed and the more accurate structures are revealed, the more this helps in the fight against these diseases."

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