Melik C. Demirel
Assistant Professor of Engineering Science and Mechanics
Pearce Development Professor
Melik Demirel considers himself both a modeler and experimentalist seeking to understand the structure and functional relationships of proteins and biomolecular assemblies. His vision is to develop computational and experimental tools that work together for the study of bio-nano materials. "We focus on biomolecular materials research using a theory-driven experimental approach," he says, "rather than trial and error." He hopes to address the pressing need to systematically elucidate the dynamics of proteins for the development of better drugs and biodetection devices by bridging the gap between molecular biology, theoretical chemistry, and materials science with techniques he has been instrumental in developing.
For example, simulating the structure and dynamics of large numbers of proteins and their complexes is a large task by any reckoning - just a small or average-sized protein such as protein-L could take several years of computational time. To compare computational results with experimental results, a more immediate solution is desirable, so a new simulation approach to the study of proteins was developed together with colleagues at the University of Pittsburgh Medical School, Polymer Research Center of Bogazici University, and the National Institutes of Health. The resulting Gaussian Network Model (GNM) technique was first presented in the 3 publications below (highly cited according to ISIhighlycited.com).
GNM simulation of a protein (a) and a protein connectivity map (b).
Chart compares experimental (thin curve) with theoretical
GNM (thick curve) temperature factors for chymotrypsin inhibitor-2 protein.
GNM is considered a breakthrough for simulation of protein molecules and describes the dynamic characteristics of proteins such as domain motions and folding patterns. HIV-1 has been accurately identified using this modeling technique, improving our understanding of its functionality and stability. Currently, GNM is also being applied to understand and predict the binding mechanisms of biological assemblies and their interactions with drugs. Other mathematical tools for computational modeling are being developed and include model testing and validation in collaboration with theoretical and experimental scientists at other universities and institutions. He is collaborating with Jorge Sofo (Physics Department) on simulation of protein structures on confined synthetic environments such as gold and silica surfaces.
Practical Applications
The design of inexpensive and sensitive biodetection devices that can be used in the doctor's office or at home for identifying diseases such as influenza as well as biotoxins are some of the applications guided by his computational efforts. Currently he is working with a potential industrial partner on a microfluidics-based device to detect pathogens, which he hopes will be another breakthrough.
Microfluidics device (~ 3.5 cm diameter) for
detecting pathogens as fabricated in
Professor Demirel's Biomolecular Materials
Laboratory and a schematic description
of a detection mechanism for use with optical probing.
A New Bio-Nano Lab, New Course Development - and Research
In addition to building his new Biomolecular Materials Laboratory, Professor Demirel has been a primary user and developer of the Penn State Lion-XM PC Cluster, a cost-effective, high-performance parallel computing system that enables faculty and other researchers to run complex computer simulation programs. Professor Demirel also has been charged with developing 2 new graduate-level courses on bio-nano materials as part of a new nano minor being proposed by Stephen Fonash (Kunkle Chair, Professor of Engineering Sciences, and Director of the Center for Nanotechnology Education and Utilization). With R-ka Albert (Physics Department), he has started a quantitative bioscience group (see schedule) that meets 2 or 3 times a month to hear presentations by researchers at Penn State and other institutions, followed by discussion. And last, but not least, he is currently preparing a chapter for a book on bio-MEMS, is working on several papers, and has a grant proposal out for simulation and design of biomolecular materials. After just 6 months at Penn State, Melik Demirel "has a lot on his plate."
Front and side views of DNA topo II (a and b) and
GyrA (c and d), crystallograhically determined simulations
utilizing Protein Data Bank (PDB) files.
Bio
He received his BS (1996) from the School of Engineering and his MS (1998) from the Institute of Graduate Studies, Bogazici University, Istanbul, Turkey. In the U.S. (1998 to 1999), he was a Laboratory of Experimental and Computational Biology (LECB) research consultant at the National Cancer Institutes at the NIH in Bethesda, MD. In 2001, he received his MS in Materials Science and Engineering from Carnegie Mellon University in Pittsburgh, PA, and completed his PhD there in 2002. During that time he was a research assistant for the Los Alamos National Laboratory Materials Science & Technology department where he went on the become a postdoctoral fellow (2002 to 2003). A few of his noteworthy awards and honors: ICAM Fellow (2003) at the Institute for Complex Adaptive Matter, Los Alamos, NM; research fellow at Alexander von Humboldt Research, Germany (2003); and he was appointed the Pearce Development Professor at Penn State in the Fall of 2003. He has been a member of the Materials Research Society (MRS) since 2000 and a member of the American Society of Engineering Educators (ASEE) since 2003. He has given numerous invited talks throughout the world.
Selected Publications on GNM
Identification of kinetically hot residues in proteins. Demirel MC, Atilgan AR, Jernigan RL, Erman B, and Bahar I. Protein Sci 7(12):2522-2532, 1998.
Vibrational dynamics of folded proteins: Significance of slow and fast motions in relation to function and stability. Bahar I, Atilgan AR, Demirel MC, and Erman B. Phys Rev Let 80(12):2733-2736, 1998.
Anisotropy of fluctuation dynamics of protein with an elastic network model. Atilgan AR, Durell SR, Jernigan RL, Demirel MC, Keskin O, and Bahar I. Biophys J 80(1):505-515, 2001.
New Nano-Bio Courses
ESC-497 Introduction to Biomolecular Materials (Spring 2004)
Students will explore advances in biomaterials-based science and technology at various length scales (nano:protein, meso:cell, micro:tissue). Basic understanding of immune responses, physics of biological assembilies, and device applications (implants, drug delivery systems, biomedical sensors) are introduced.
ESC-497 Simulation and Design of Nanostructures (Fall 2004)
Students will learn simulation techniques and design rules for nanostructures. Basic concepts of computer modeling will be introduced using quantum and classical approaches. Fundamental physical phenomena encountered in the molecular fields of computational physics, chemistry, and biology will be studied. Applications are drawn from a broad range of fields including soft and condensed matter to build an understanding of nanostructures.
