Abstract: 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 molecular
dynamics (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
 and a mechanosensitive channel  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
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  and a DNA fragment labeled simultaneously with two spin labels .
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 E. Perozo, D. M. Cortes, and L. G. Cuello. Structural Rearrangements Underlying K+-Channel Activation Gating. Science, 285:73–78, 1999.
 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.
 Deniz Sezer, Jack H. Freed, and Benoˆıt 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.
 Deniz Sezer and Snorri Th. Sigurdsson. Simulating electron spin resonance spectra of macromolecules labeled with two dipolar-coupled nitroxide spin labels from trajectories (submitted).
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. Benoˆıt 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.