FENS Seminars – Asst. Prof. Sefer Baday
Asst. Prof. Sefer Baday (İstanbul Technical University) will be the guest of KHAS Faculty of Engineering and Natural Sciences seminar with his speech “Molecular Dynamics Simulations of Proteins in the Perspective of Drug Resistance and Novel Drug Molecule Development” on Friday, March 10 at 2 pm. The event will take place on Zoom and is open to anyone interested.
Zoom Link: https://bit.ly/3F3fMV9
Abstract: The first part of the talk will be about drug resistance in prostate cancer. Several drug molecules have been developed for the treatment of prostate cancer. Among those, Enzalutamide molecule is the most recent and potent one. In clinical studies, Enzalutamide therapy reduced significantly radiographic progression and delayed the need for chemotherapy. Despite this success, recently it has been discovered that drug resistance against Enzalutamide occurred. Development and progression of the prostate cancer depends on the androgen stimulation. Therefore, antiandrogen drug molecules target and inhibit Androgen Receptor (AR) signaling function. Enzalutamide properly inhibits AR signaling in wild-type ARs, however a point mutation F876L abolishes the antagonistic activity of enzalutamide. The molecular mechanisms of this resistance remain elusive. Thus, we investigated the mechanism of this resistance at the molecular level using Molecular Dynamics (MD) simulations. The second part of the talk will be on Ryanodine receptors (RyRs). These receptors are large (around 20 MDa) homotetrameric intracellular ion channels. RyRs are located in the membrane of the sarcoplasmic reticulum (SR). RyRs play a central role in the excitation-contraction coupling by regulating Ca2+ release from the SR to the cytosol. Dysregulation of RyRs leads to abnormal cellular activity. Dantrolene is an approved muscle relaxant used for the treatment of malignant hyperthermia that occurs by dysregulation of RyR1. However, mechanism of action of dantrolene molecule is not known. Using molecular docking and simulations, we tried to understand how dantrolene inhibits RyR receptors. The last part of the talk will be on designing novel mitochondrial fission inhibitors targeting Drp1-GTPase interaction using computational methods. Here, 3 million molecules were screened using a series of docking and MD simulations. Among the predicted molecules, three molecules were shown to be active to inhibit mitochondrial fission.
About the Speaker: Dr. Baday works as an assistant professor in the Informatics Institute of Istanbul Technical University, Turkey. He has chemical engineering BS and Computational science and engineering MS degrees from Bogazici and Koc Universities in Turkey. He obtained his PhD degree from the University of Basel, Switzerland. Prior to the current appointment, he had worked as a researcher in the University of Cambridge UK. His research is based on the application of molecular modelling, simulation and informatics approaches for drug discovery.