Seminars 13th April_2

The Ethics of Science and Engineering

ITU Electirics and Electronics Faculty 13 April 2011

Seminars 13th April_1

Bogazici University Physics Department, Feza Gursey Seminar Room

13 April 2011 Wednesday 15:30

Deniz Sezer, Sabancı University

Towards understanding of protein conformational changes through simulations of biomolecular and spin dynamics.

One of the most ambitious aims in molecular biophysics?pursued both experimentally and theoretically?is to understand in atomistic detail the functionally relevant conformational transitions of biological molecules. More specifically, the goal is to identify the relevant conformations on the basis of their free energies and to characterize the sequence and time scales of the transitions between these conformations. In principle, this could be achieved computationally through moleculardynamics (MD) simulations. In practice, MD simulations, like any other model, rely on approximations and have their own inherent limitations. Therefore, direct comparison of the MD simulations with experimental data is essential. Among the experimental methods that probe the structure and dynamics of biomolecules electron spin resonance (ESR) spectroscopy provides rich information [1-3]. For example, ESR spectroscopy revealed the open conformations of a potassium channel [4] and a mechanosensitive channel [5] for which only the closed conformations were available from X-ray crystallography. In spite of the utility of ESR spectra, however, their interpretation in terms of the underlying molecular properties is not always unambiguous.

In this talk I will argue that the atomistic picture required for the conclusive interpretation of ESR data can be effectively obtained from MD simulations. In return, the experimental spectra can provide a stringent validation of the MD simulations, thus addressing concerns regarding their limitations. An unambiguous, quantitative comparison of these two techniques can be achieved by calculating the measured ESR spectra directly from the MD simulations. Naturally, such prediction of ESR spectra from ?first principles? poses many challenges. The systematic approach followed in addressing these challenges will be presented. The developed methodology will be illustrated in the context of a spin-labeled protein [6] and a DNA fragment labeled simultaneously with two spin labels [7].
[1] P. P. Borbat, A. J. Costa-Filho, K. A. Earle, J. K. Moscicki, and J. H. Freed. Electron spin resonance in studies of membranes and proteins. Science, 291:266-269, 2001.
[2] Linda Columbus and Wayne L. Hubbell. A new spin on protein dynamics. TIBS, 27:288-295, 2002.
[3] Gail E. Fanucci and David S. Cafiso. Recent advances and applications of site-directed spin labeling. Curr. Opin. Struct. Biol., 16:644-653, 2006.
[4] E. Perozo, D. M. Cortes, and L. G. Cuello. Structural Rearrangements Underlying K+-Channel Activation Gating. Science, 285:73?78, 1999.
[5] E. Perozo, D. M. Cortes, P. Sompornpisut, A. Kloda, and B. Martinac. Open channel structure of MscL and the gating mechanism of mechanosensitive channels. Nature, 418:942?948, 2002.
[6] Deniz Sezer, Jack H. Freed, and Beno?ıt Roux. Multifrequency electron spin resonance spectra of a spin-labeled protein calculated from molecular dynamics simulations. J. Am. Chem. Soc., 131(7): 2597-2605, 2009.
[7] Deniz Sezer and Snorri Th. Sigurdsson. Simulating electron spin resonance spectra of macromolecules labeled with two dipolar-coupled nitroxide spin labels from trajectories (submitted).

Biographical sketch
Deniz Sezer studied Electrical Engineering and Physics at Bo?gazi¸ci University, graduating in 1998. He obtained his Master?s degree in Physics from the same university in 2000. Between 2000 and 2008 he was a graduate student in the Physics department at Cornell University. During this period he worked successively at the following departments (institutions): Physics (Cornell University), Physiology and Biophysics (Graduate School of Medical Sciences of Cornell University), and Biochemistry and Molecular Biology (The University of Chicago). His PhD research was conducted in the group of Prof. Beno?ıt Roux, who is mostly known for his computational work on potassium channels. From early 2008 until the end of 2009 Deniz was a postdoctoral researcher in the Institute of Physical and Theoretical Chemistry at the University of Frankfurt. There he worked in the group of Prof. Thomas Prisner, who is pushing the limits of electron spin resonance (ESR) spectroscopy by developing new methodologies for the characterization of biomolecular systems. Since February 2010 Deniz is a faculty member in the Faculty of Engineering and Natural Sciences at Sabancı University, where he teaches courses in Structural Biology, Biophysics, and Mathematical Methods for Scientists and Engineers. During both his doctoral and postdoctoral research Deniz worked on the development of computational tools that make possible the interpretation of ESR experiments of biomolecules in terms of their atomic structure and dynamics. He continues working in this direction at Sabancı University.

Seminars 24th January

Biomedical Engineering Seminars’ speaker was  Kamuran KADIPAŞAOĞLU and this  has been the most incentive part of these meetings.

Image Source: Bahcesehir University

Seminars 4th November

Prof. Nelson Y.S. Kiang

The Speech and Hearing Bioscience and Technology PhD program in the Harvard-MIT Division of Health Sciences and Technology is an interdisciplinary training program designed to produce the next generation of pioneers in basic and clinical speech and hearing research. The program was established in 1992 by Nelson Kiang, and is currently co-directed by Drs. Louis Braida and Bertrand Delgutte.

As of 2006, the program has graduated about 60 PhD students in nearly all areas of speech and hearing research: auditory mechanics, peripheral and central auditory neuroscience, auditory psychophysics, hearing aids/cochlear implants, speech perception and production, machine processing of speech, language processing, voice disorders/laryngeal physiology, and vestibular physiology.

There are about 50 faculty members in the SHBT program, most of which hold appointments at MIT or Harvard Medical School. The main laboratories are at MIT, Harvard, the Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital, Brigham and Women’s Hospital, Children’s Hospital, Boston University, and Northeastern University.