International Grant Awarded to ITU Faculty Member Mert Gür in Fight Against Coronavirus

by İTÜ | Apr 08, 2020
Dr. Mert Gür, from Mechanical Engineering Department, and his collaborators have been named recipients of two prestigious research awards from the USA and the European Union (EU), in both of which Mert Gür will be acting as principal investigator. The research project titled “Investigation of the Cell Attachment and Fusion Mechanism of the SARS-CoV-2 Spike Glycoprotein Using Molecular Dynamics Simulations” by Dr. Gür in collaboration with UC Berkeley is expected to contribute significantly to global research on developing drugs within the scope of the fight against the New Coronavirus.

International Grant Awarded to ITU Faculty Member Mert Gür in Fight Against Coronavirus

Dr. Mert Gür of Mechanical Engineering Department, who was awarded the Outstanding Young Scientist Award (GEBİP) by the Turkish Academy of Sciences (TUBA)  in 2016, stated the following regarding the international support: “Prior to receiving this prestigious award, we explored for the first time in literature the activation mechanism of the protein responsible for Coronavirus binding to human cells at all-atom resolution via extensive Molecular Dynamics simulations, which remained to be explored at full detail prior to our study. All simulations were performed at the ITU National High Performance Computing Center (UHeM) and we are now more than halfway through the manuscript writing process”,

Two  prestigious grants awarded from the USA and the EU!

Dr. Gür emphasized that their joint research proposal with UC Berkeley on Coronavirus research was awarded in just 2 days after their application to the grant call spearheaded by the US White House Office of Science and Technology Policy, the U.S. Department of Energy and IBM. Furthermore, Dr. Gür added, “In addition, our proposal in collaboration with UC Berkeley and MRC Laboratory of Molecular Biology on dynein motor proteins , which are exceptionally  critical for the future of nanotechnology, was awarded with a massive grant by the Partnership for Advanced Computing in Europe. In total, the two grants provide us 73.400.000,00 core hours of computer resources, which is a colossal amount of computing resources.” 

Dr. Mert Gür answered the questions of ITU News regarding both projects.

What are the titles of the projects?

“Exploring Binding and Fusion Mechanism of SARS-CoV-2 Spike Glycoprotein Using Molecular Dynamics Simulations.”


 “Modeling the Mechanochemical Cycle of the Cytoplasmic Dynein Motor Protein.”

Why are these project needed? What is the motivation behind them?

Novel coronavirus cases and deaths are increasing exponentially all over the world. Although research studies have been performed globally, no effective drug against the Novel Coronavirus has yet been developed. Therefore, there is an urgent need to develop drugs with new and novel mechanisms of action. In order to address this need, it is necessary to explore the functional mechanism of the protein that enables coronavirus to bind to and fuse with human cells (which is a mechanism yet to be elucidated) with all of its atomic details. By doing so, novel drug designs will be possible that block the functional mechanism of protein and hence prevent the disease.

Regarding our other project, cytoplasmic dynein motor protein has a strong potential to play a critical role in the future of nanotechnology. Furthermore, loss of dynein function has been associated with numerous diseases. Proteins are nanomachines found in nature. Various proteins in the human body, such as pumps, transporters and motor proteins, have complex operating mechanisms and these mechanisms are directly comparable to the machines we encounter in our daily lives. These proteins convert various types of energies into work and operate on thermodynamic cycles. Dynein motor proteins are magnificent nanomachines which transport cargos by walking on microtubules within the cell. Microtubules can be thought as roads and streets inside the cell. The energy input of the dynein nanomachine, i.e. the fuel required to power the machine, is the ATP molecule. In car engines, combustion of fossil fuels generates heat which is then converted to mechanical work. Similarly, in dynein nanomachines, ATP hydrolysis takes place releasing free energy and this energy is converted into mechanical work which provides the movement of the nanomachine. The distinct feature that separates dyneins from other motor proteins and makes it unique for nanotechnological applications is that it has a structurally distinct motor domain and a unique microtubule binding domain. Thus, it is theoretically possible to incorporate the dynein motor domain into a designed nanomachines to power it. In addition, as we have shown in our recent article published in Nature, it is possible to alter the operating mechanism of the dynein nanomachines by applying protein engineering. Thus, making repurposing of dynein also a promising strategy for nanotechnological applications.

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What are you aiming with the projects?

Spike protein, which is located on the coronavirus surface, first binds to the ACE2 receptor of human cell. Upon binding, spike protein facilitates fusion of virus and cell membranes by undergoing large scale conformational changes. As a result, the virus is able to inject its genetic material to enter the human cell and, by doing so, the human cells become infected with the virus. The aim of this project is to determine novel therapeutic strategies that could prevent this mechanism at any step during its functional cycle. To this aim, the binding of the spike protein to its receptor, the structural changes it undergoes and its interactions with the cell membrane will be modeled in real time with Molecular Dynamics Simulations under physiological conditions for the first time in literature.

The goal of our other project is to perform state of art Molecular Dynamics simulations to explore the structural changes, dynamics, and energetics of the cytoplasmic dynein machinery at all-atom resolution. These simulations will provide unique insight and information regarding the operating mechanism and principles of the motor domain, which provides mechanical motion of the nanomachine, and the micro tubule binding domain, which facilitates movement along the microtubule. By doing so, we aim to reveal details and characteristics of the mechanical parts and machinery of dynein that can be directly applied to nanotechnological applications.

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How long will the project take? What data did you use?

Due to the importance and urgency of the matter, our project on Coronavirus aims to be performed within 3 months. Our project on dynein nanomachines, on the other hand, will be performed within a year. In both projects, data unprecedented in size and extend regarding the proteins functional mechanism will be produced in three of the world’s most advanced and powerful supercomputers using hundreds of processors (thousands of cores) simultaneously. 

What would you like to say about the social benefits of the project and in particular in terms of encouraging the scientific world?

The number of epidemic diseases encountered in the 21st century keeps increasing and scientists predict a continuation of this trend in the upcoming years. Our study will significantly contribute to the rapid and effective discovery of novel drug targets alternative to traditional ones. Thus, the project will make a particularly important contribution to the world’s fight against Coronavirus.

In recent years, the application areas of nanotechnology have increased at an extraordinary rate and have gained an undeniable place in our daily life. As knowledge and accumulation of nanotechnology increases, it seems that it is more effective to apply the highly effective and highly efficient biological nanomechanisms working mechanisms already existing in nature, rather than developing nanomechanisms from scratch. Dynein proteins will make a great contribution to the future of nanotechnology as it is among the most suitable nanomechanisms for nanotechnology applications.

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About Dr. Mert Gür

Assist. Prof. Dr. Mert Gur earned his Bachelor’s degree from the Department of Mechanical Engineering Department at Middle East Technical University in 2006 and his PhD degree in Computational Science and Engineering at Koç University in 2010. Following his graduation, he was awarded the position of a postdoctoral associate in the Department of Computational and Systems Biology at the University of Pittsburgh’s School of Medicine. During his time in this position, he became jointly appointed as a Lecturer in the Department of Mechanical Engineering and Material Science of the same university. In 2014, Dr. Gur joined the Joint Center for Artificial Photosynthesis (JCAP) at Lawrence Berkeley National Laboratory as a postdoctoral fellow. In 2015, he was appointed as a Faculty member at the rank of assistant professor in the ITU Faculty/School of Mechanical Engineering. He worked as a visiting faculty scholar in the Department of Computational and Systems Biology at the University of Pittsburgh’s School of Medicine in 2016. Mert Gur performed research as a visiting scholar in the Chemistry Department at UC Berkeley in 2017. Dr. Gur was appointed as the Vice Dean of Graduate School of Science, Engineering and Technology in 2018 and as the Vice Dean of Faculty of Mechanical Engineering in 2020, respectively.  Since 2019, he is also acting as the Advisory Committee Member and Business Development Advisor to the Director of National High Performance Computing Center (UHeM). So far, he has published a book chapter and 21 journal papers including Nature, Nature Communications, JBC, JCP, BJ, EBioMedicine and PLoS Bio. Mert Gur joined the editorial board of Journal of Molecular Graphics and Modelling in 2016. Mert Gur was elected to receive the Turkish Academy of Sciences (TÜBA) Outstanding Young Scientist (GEBİP) Award in 2016.