Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery: Bridging Experiments and Computations - September 10-14, 2014, Istanbul, Turkey

Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Poster Session II

60-POS Board 13 Internal Dynamics of DHFR Revealed by Simulated Shock Waves Propagation Franci Merzel 1 , Erika Balog 2 . 1 National Institute of Chemistry, Ljubljana, Slovenia, 2 Semmelweis University, Budapest, Hungary. It has been demonstrated that the adiabatic compressibility (AC) is a useful measure of the conformational flexibility of proteins in different functional forms. Binding of various ligands to dihydrofolate reductase (DHFR) gives rise to large differences in AC. Moreover, neutron scattering experiments have shown that binding of the cancer drug methotrexate softens the low- frequency vibrations of its target protein DHFR. Here, using non-equilibrium molecular dynamics simulations of the response of DHFR to the shock waves at various incident angles we explore the relationship between the population and directionality of the protein low frequency vibrational modes and AC. We identify protein dynamics characteristics that might be critical for enzyme function of DHFR. 61-POS Board 14 Neutron Spectroscopic Bbservation of Fast Motions in ADH with and without NAD in Aqueous Solution. Michael Monkenbusch 1 , Andreas Stadler 2 , Biehl Ralf 2 , Jacques Ollivier 3 , Michaela Zamponi 4 , Dieter Richter 2 . 1 FZ-Juelich, Juelich, Germany, 2 FZ-Juelich, Juelich, Germany, 4 FZ-Juelich, Garching, Germany. 3 Institut Laue Langevin, Grenoble, France, Covering the range from nanoseconds to picoseconds and several nanometer to Angstroems high resolution inelastic neutron yields information on large scale domain motions in a protein as well as more local protein dynamics. Results from high resolution time-of-flight spectroscopy and neutron backscattering spectroscopy from a 5% solution of alcohol dehydrogenase ADH with and without NAD in a deuterated buffer solution are presented. Whereas the large scale domain motions are significant to facilitate incorporation of the NAD cofactor [Biel et al.,PRL 101, 138102] the question remains how the fast more local dynamical features correlate with function, resp. incorporation of NAD. Local protein dynamics on top of the large scale diffusional and domain motions have been observed. A fraction of about 1/3 of the non-exchangable protons in the protein show high mobility with large amplitudes of several Angstroems. Indications are seen that the association of NAD reduces this mobilty.

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