5 results on '"Oktay Gocenler"'
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2. Case Study of High-Throughput Drug Screening and Remote Data Collection for SARS-CoV-2 Main Protease by Using Serial Femtosecond X-ray Crystallography
- Author
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Omur Guven, Mehmet Gul, Esra Ayan, J Austin Johnson, Baris Cakilkaya, Gozde Usta, Fatma Betul Ertem, Nurettin Tokay, Busra Yuksel, Oktay Gocenler, Cengizhan Buyukdag, Sabine Botha, Gihan Ketawala, Zhen Su, Brandon Hayes, Frederic Poitevin, Alexander Batyuk, Chun Hong Yoon, Christopher Kupitz, Serdar Durdagi, Raymond G. Sierra, and Hasan DeMirci
- Subjects
SARS-CoV-2 ,main protease ,serial femtosecond crystallography ,high-throughput drug screening ,Crystallography ,QD901-999 - Abstract
Since early 2020, COVID-19 has grown to affect the lives of billions globally. A worldwide investigation has been ongoing for characterizing the virus and also for finding an effective drug and developing vaccines. As time has been of the essence, a crucial part of this research has been drug repurposing; therefore, confirmation of in silico drug screening studies have been carried out for this purpose. Here we demonstrated the possibility of screening a variety of drugs efficiently by leveraging a high data collection rate of 120 images/second with the new low-noise, high dynamic range ePix10k2M Pixel Array Detector installed at the Macromolecular Femtosecond Crystallography (MFX) instrument at the Linac Coherent Light Source (LCLS). The X-ray Free-Electron Laser (XFEL) is used for remote high-throughput data collection for drug repurposing of the main protease (Mpro) of SARS-CoV-2 at ambient temperature with mitigated X-ray radiation damage. We obtained multiple structures soaked with nine drug candidate molecules in two crystal forms. Although our drug binding attempts failed, we successfully established a high-throughput Serial Femtosecond X-ray crystallographic (SFX) data collection protocol.
- Published
- 2021
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3. Characterizing the Monomer–Dimer Equilibrium of UbcH8/Ube2L6: A Combined SAXS and NMR Study
- Author
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Kerem Kahraman, Scott A. Robson, Oktay Göcenler, Cansu M. Yenici, Cansu D. Tozkoparan Ceylan, Jennifer M. Klein, Volker Dötsch, Emine Sonay Elgin, Arthur L. Haas, Joshua J. Ziarek, and Çağdaş Dağ
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Chemistry ,QD1-999 - Published
- 2024
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4. Near-physiological-temperature serial crystallography reveals conformations of SARS-CoV-2 main protease active site for improved drug repurposing
- Author
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Gunseli Yildirim, Alaleh Shafiei, Oleksandr Yefanov, Hasan DeMirci, Frédéric Poitevin, Timucin Avsar, Chun Hong Yoon, Muge Didem Orhan, Merve Yigin, Lalehan Oktay, Fulya Aksit, Çağdaş Dağ, Serdar Durdagi, Christopher Kupitz, Omur Guven, Valerio Mariani, Ece Erdemoglu, Ebru Destan, Edward H. Snell, Ismail Erol, Mark S. Hunter, Esra Ayan, Berna Dogan, Mengning Liang, Busecan Aksoydan, A. Batyuk, Ozgur Can, Cengizhan Buyukdag, Sabri O. Besler, Seyma Calis, Brandon Hayes, Matthew Seaberg, Serena Ozabrahamyan, Ilayda Tolu, Gihan K. Ketawala, Anton Barty, Raymond G. Sierra, Kader Sahin, Gokhan Tanisali, Oktay Gocenler, Ali D. Yucel, E. Han Dao, Alpsu Olkan, Ayse B. Peksen, Zhen Su, A. Tolstikova, Sabine Botha, Busra Yuksel, Fatma Betul Ertem, Demirci, Hasan (ORCID 0000-0002-9135-5397 & YÖK ID 307350), Dağ, Çağdaş, Yığın, Merve, Büyükdağ, Cengizhan, Ertem, Fatma Betül, Yıldırım, Günseli, Destan, Ebru, Güven, Ömür, Ayan, Esra, Yüksel, Büşra, Pekşen, Ayşe Buket, Göçenler, Oktay, Yücel, Ali Doğa, Can, Özgür, Ozabrahamyan, Serena, Shafiei, Alaleh, Akşit, Fulya, Tanısalı, Gökhan, Besler, Sabri Özkan, Durdağı, Serdar, Doğan, Berna, Avşar, Timuçin, Erol, İsmail, Çalış, Şeyma, Orhan, Müge D., Aksoydan, Busecan, Şahin, Kader, Oktay, Lalehan, Tolu, İlayda, Olkan, Alpsu, Erdemoğlu, Ece, Yefanov, Oleksandr M., Dao, E. Han, Hayes, Brandon, Liang, Mengning, Seaberg, Matthew H., Hunter, Mark S., Batyuk, Alex, Mariani, Valerio, Su, Zhen, Poitevin, Frederic, Yoon, Chun Hong, Kupitz, Christopher, Sierra, Raymond G., Snell, Edward H., Koç Üniversitesi İş Bankası Enfeksiyon Hastalıkları Uygulama ve Araştırma Merkezi (EHAM) / Koç University İşbank Center for Infectious Diseases (KU-IS CID), College of Sciences, Graduate School of Sciences and Engineering, School of Nursing, Department of Molecular Biology and Genetics, Department of Chemical and Biological Engineering, and Department of Materials Science and Engineering
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Drug ,Molecular model ,Protein Conformation ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,media_common.quotation_subject ,medicine.medical_treatment ,ambient temperature ,Molecular Conformation ,Crystallography, X-Ray ,Article ,Structural Biology ,Catalytic Domain ,medicine ,SFX ,Computer Simulation ,Molecular Biology ,Coronavirus 3C Proteases ,media_common ,Principal Component Analysis ,Protease ,Biochemistry and molecular biology ,Biophysics ,Cell biology ,biology ,drug repurposing ,Drug discovery ,SARS-CoV-2 ,Drug Repositioning ,Temperature ,Active site ,Small molecule ,Recombinant Proteins ,COVID-19 Drug Treatment ,Molecular Docking Simulation ,Drug repositioning ,Crystallography ,main protease ,Drug Design ,ddc:540 ,biology.protein ,Dimerization ,Ambient temperature ,Drug repurposing ,Main protease - Abstract
The COVID-19 pandemic has resulted in 198 million reported infections and more than 4 million deaths as of July 2021 (covid19.who.int). Research to identify effective therapies for COVID-19 includes: (1) designing a vaccine as future protection; (2) de novo drug discovery; and (3) identifying existing drugs to repurpose them as effective and immediate treatments. To assist in drug repurposing and design, we determine two apo structures of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease at ambient temperature by serial femtosecond X-ray crystallography. We employ detailed molecular simulations of selected known main protease inhibitors with the structures and compare binding modes and energies. The combined structural and molecular modeling studies not only reveal the dynamics of small molecules targeting the main protease but also provide invaluable opportunities for drug repurposing and structure-based drug design strategies against SARS-CoV-2., Graphical abstract, Durdağı et al. represent radiation damage-free high-resolution SARS-CoV-2 main protease SFX structures obtained at near-physiological temperature and performed MD simulation of apo-form proteins and three known main protease inhibitors. The structures reveal alternate conformation, while MD simulation indicates asymmetric behavior of the protein, which is invaluable information for immediate drug-repurposing studies.
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- 2021
- Full Text
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5. Near-Physiological-Temperature Serial Femtosecond X-ray Crystallography Reveals Novel Conformations of SARS-CoV-2 Main Protease Active Site for Improved Drug Repurposing
- Author
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Christopher Kupitz, Oleksandr Yefanov, Ilayda Tolu, Berna Dogan, Chun Hong Yoon, A. Tolstikova, Sabri O. Besler, Edward H. Snell, Busra Yuksel, Ismail Erol, Mark S. Hunter, Merve Yigin, Lalehan Oktay, Fulya Aksit, Çağdaş Dağ, Ece Erdemoglu, Brandon Hayes, Betul Ertem, Raymond G. Sierra, Omur Guven, Seyma Calis, Alaleh Shafiei, Zhen Su, Serena Ozabrahamyan, Oktay Gocenler, Gihan K. Ketawala, A. Batyuk, Valerio Mariani, Gunseli Yildirim, Kader Sahin, Esra Ayan, Ozgur Can, Cengizhan Buyukdag, Busecan Aksoydan, Mengning Liang, Frédéric Poitevin, Gokhan Tanisali, Alpsu Olkan, E. Han Dao, Ayse B. Peksen, Anton Barty, Sabine Botha, Ali D. Yucel, Matthew Seaberg, Serdar Durdagi, Ebru Destan, Muge Didem Orhan, Hasan DeMirci, and Timucin Avsar
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Drug ,Protease ,biology ,Molecular model ,Chemistry ,media_common.quotation_subject ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,medicine.medical_treatment ,Active site ,Computational biology ,Small molecule ,Drug repositioning ,Structural biology ,biology.protein ,medicine ,media_common - Abstract
The COVID19 pandemic has resulted in 25+ million reported infections and nearly 850.000 deaths. Research to identify effective therapies for COVID19 includes: i) designing a vaccine as future protection; ii) structure-based drug design; and iii) identifying existing drugs to repurpose them as effective and immediate treatments. To assist in drug repurposing and design, we determined two apo structures of Severe Acute Respiratory Syndrome CoronaVirus-2 main protease at ambienttemperature by Serial Femtosecond X-ray crystallography. We employed detailed molecular simulations of selected known main protease inhibitors with the structures and compared binding modes and energies. The combined structural biology and molecular modeling studies not only reveal the dynamics of small molecules targeting main protease but will also provide invaluable opportunities for drug repurposing and structure-based drug design studies against SARS-CoV-2.One Sentence SummaryRadiation-damage-free high-resolution SARS-CoV-2 main protease SFX structures obtained at near-physiological-temperature offer invaluable information for immediate drug-repurposing studies for the treatment of COVID19.
- Published
- 2020
- Full Text
- View/download PDF
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