115
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.
