Bulletin of the American Physical Society
APS March Meeting 2014
Volume 59, Number 1
Monday–Friday, March 3–7, 2014; Denver, Colorado
Session W32: Invited Session: Quantum Mechanics Applied to Biophysical Problems |
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Sponsoring Units: DCOMP DBIO Chair: Susan Rempe, Sandia National Laboratories Room: 708-712 |
Thursday, March 6, 2014 2:30PM - 3:06PM |
W32.00001: Principles Governing Metal Ion Selectivity in Ion Channel Proteins Invited Speaker: Carmay Lim Our research interests are to \begin{enumerate} \item (i) unravel the principles governing biological processes and use them to identify novel drug targets and guide drug design, and \item (ii) develop new methods for studying macromolecular interactions. \end{enumerate} This talk will provide an overview of our work in these two areas and an example of how our studies have helped to unravel the principles underlying the conversion of Ca$^{2+}$-selective to Na$^{+}$-selective channels. Ion selectivity of four-domain voltage-gated Ca$^{2+}$(Ca$_{\mathrm{v}})$ and sodium (Na$_{\mathrm{v}})$ channels, which is controlled by the selectivity filter (SF, the narrowest region of an open pore), is crucial for electrical signaling. Over billions of years of evolution, mutation of the Glu from domain II/III in the \textbf{EEEE}/\textbf{DEEA} SF of Ca$^{2+}$-selective Ca$_{\mathrm{v}}$ channels to Lys made these channels Na$^{+}$-selective. This talk will delineate the physical principles why Lys is sufficient for Na$^{+}$/Ca$^{2+}$selectivity and why the \textbf{DEKA} SF is more Na$^{+}$-selective than the \textbf{DKEA} one. \\[4pt] References:\\[0pt] [1] Competition among metal ions for protein binding sites: Determinants of metal ion selectivity in proteins. Todor Dudev {\&} Carmay Lim, \textit{Chemical Reviews} (\textbf{2013}) http://dx.doi.org/10.1021/cr4004665\\[0pt] [2] Effect of Metal Hydration on the Selectivity of Mg$^{2+}$ vs. Ca$^{2+}$ in Magnesium Ion Channels. Todor Dudev {\&} Carmay Lim \textit{J. Am. Chem. Soc.}\textbf{ (2013) }\underline {135}: 17200-17208. \\[0pt] [3] Competition among Ca$^{\mathrm{2+}}$, Mg$^{2+}$, and Na$^{+}$ for ion channel selectivity filters: Determinants of metal ion selectivity. Todor Dudev {\&} Carmay Lim,$ J$. \textit{Phys. Chem. B} (\textbf{2012)} \underline {116}: 10703--10714.\\[0pt] [4] Why voltage-gated Ca$^{2+}$ and bacterial Na$^{+}$ channels with the same EEEE motif in their selectivity filters confer opposite metal selectivity. Todor Dudev {\&} Carmay Lim,\textit{ Phys. Chem. Chem. Phys. }(\textbf{2012)}\underline { 14}: 12451--12456. [Preview Abstract] |
Thursday, March 6, 2014 3:06PM - 3:42PM |
W32.00002: Quantum Mechanical Studies of Asparaginase Reaction Invited Speaker: Maria J. Ramos |
Thursday, March 6, 2014 3:42PM - 4:18PM |
W32.00003: Free Energy Wells and Barriers to Ion Transport Across Membranes Invited Speaker: Susan Rempe The flow of ions across cellular membranes is essential to many biological processes. Ion transport is also important in synthetic materials used as battery electrolytes. Transport often involves specific ions and fast conduction. To achieve those properties, ion conduction pathways must solvate specific ions by just the ``right amount.'' The right amount of solvation avoids ion traps due to deep free energy wells, and avoids ion block due to high free energy barriers. Ion channel proteins in cellular membranes demonstrate this subtle balance in solvation of specific ions. Using ab initio molecular simulations, we have interrogated the link between binding site structure and ion solvation free energies in biological ion binding sites. Our results emphasize the surprisingly important role of the environment that surrounds ion-binding sites for fast transport of specific ions. [Preview Abstract] |
Thursday, March 6, 2014 4:18PM - 4:54PM |
W32.00004: An Unusual Co(I)--H Interaction: Structural and Mechanistic Ramifications for Methyltransferases Invited Speaker: Manoj Kumar The cob(II)alamin cob(I)alamin (Co$^{2+}$/Co$^{1+})$ reduction is a common chemical event in a broad family of cytoplasmic methyltransferases and ATP:corrinoid adenosyltransferases, respectively. Despite its broad and general chemical appeal, the Co$^{2+}$/Co$^{1+}$ reduction continues to remain one of the least understood aspects of corrinoid chemistry. This is due in part to the inaccessible redox chemistry of Co$^{2+}$/Co$^{1+}$ couple under cellular conditions i.e., the reduction potential of cob(II)alamin (-500 mV vs SHE) is more negative than that of the common physiological reductants (-280 mV to -440 mV vs SHE) present in the cellular environments. To gain better understanding about the Co$^{2+}$/Co$^{1+}$ reduction, we have utilized the density functional theory and quantum mechanics/molecular mechanics (QM/MM) computational methods. The calculations indicate that cob(I)alamin, a ubiquitous B$_{12}$ intermediate, is not square planar as has been commonly accepted, but a square pyramidal species due to the unusual hydrogen bonding interaction between the Co$^{1+}$ ion and its axial ligands (\textit{Angew. Chem. Int. Ed.} \textbf{2011}, \textit{50}, 8702-8705; \textit{Inorg. Chem. }\textbf{2012}, \textit{51}, 5533-5538). The Co$^{1+}$--H interaction exerts an anodic shift of 100 mV vs SHE upon the reduction potential of the Co$^{2+}$/Co$^{1+}$ couple, which explains why this redox process is observed inside transferases. Building upon these new insights, an alternate mechanism for the enzyme-bound Co$^{2+}$/Co$^{1+}$ redox process is suggested that is mediated by the square pyramidal cob(I)alamin rather than its commonly accepted square planar analogue. [Preview Abstract] |
Thursday, March 6, 2014 4:54PM - 5:30PM |
W32.00005: From Computational Photobiology to the Design of Vibrationally Coherent Molecular Devices and Motors Invited Speaker: Massimo Olivucci In the past multi-configurational quantum chemical computations coupled with molecular mechanics force fields have been employed to investigate spectroscopic, thermal and photochemical properties of visual pigments. [1,2] Here we show how the same computational technology can nowadays be used to design, characterize and ultimately, prepare light-driven molecular switches which mimics the photophysics of the visual pigment bovine rhodopsin (Rh) [2,3]. When embedded in the protein cavity the chromophore of Rh undergoes an ultrafast and coherent photoisomerization. In order to design a synthetic chromophore displaying similar properties in common solvents, we recently focused on indanylidene-pyrroline (NAIP) systems. [3,4] We found that these systems display light-induced ground state coherent vibrational motion similar to the one detected in Rh. Semi-classical trajectories provide a mechanistic description of the structural changes associated to the observed coherent motion which is shown to be ultimately due to periodic changes in the $\pi $-conjugation. \\[4pt] [1] I. Schapiro, M. N. Ryazantsev, L. M. Frutos, N. Ferr\'{e}, R. Lindh {\&} M. Olivucci; \textit{J Am Chem Soc }\textbf{2011}\textit{, 133}, 3354. \\[0pt] [2] S. Gozem, I. Schapiro, N. Ferr\'{e}, M. Olivucci; \textit{Science} \textbf{2012}, \textit{337}, 1225.\\[0pt] [3] A. Melloni, R. Rossi Paccani, D. Donati, V. Zanirato, A. Sinicropi, M. L. Parisi, E. Martin, M. Ryazantsev, W. J. Ding, L. M. Frutos, R. Basosi, S. Fusi, L. Latterini, N. Ferr\'{e}, M. Olivucci; \textit{J Am Chem Soc} \textbf{2010},\textit{ 132}, 9310. \\[0pt] [4] J. L\'{e}onard, I. Schapiro, J. Briand, S. Fusi, R. Rossi Paccani, M. Olivucci, S. Haacke \textit{Chem Eur J }\textbf{2012}, \textit{18}, 15296. [Preview Abstract] |
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