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APPLICATION FOR INTERDISCIPLINARY RESEARCH GROUP
Molecular Mechanisms of Retinal Protein Action A
Combination of Theoretical Approaches
Most Prominent Retinal Proteins available at
atomic resolution
Complexity of Structures/Processes ? Multiscaling
Approaches
Reasoning for Establishment of the Research Group


Highly complex large scale systems
bR so far best studied retinal protein Model
structure for most elementary cell activity ion
transport
All applying groups are actively working on
modelling of biomolecular systems including
structural dynamics and functions. The groups
introduce into the consortium expertise in
applying complementary computational methods
rangeing from highly sophisticated quantum
chemistry, through ab initio DFT, semiempirical
schemes, Molecular Mechanics to Continuum
Electrostatics and interfacing these different
approaches with each other. Additionally in a
recent collaborative research effort the
Paderborn and DKFZ Heidelberg groups have
developed an approximate Density Functional
Theory (see below) that combines the accuracy of
ab initio calculations with the efficiency of
semiempirical methods. The method is generalized
to all advanced implementations of modern DFT
including time-dependent linear response TDDFT
and nonadiabatic elecron-ion dynamics with
incorporation of radiation fields.
Rich diversity of chemical reactions involved
Reactions at various extend follow different time
scales
?
Involvement of broad range of modelling approaches
ultrafast photoisomerization of retinal by
controlling PA at lysine N during photocycle ?
pumps protons against electrochemical potential
bR-functioning as photosynthetic center
Need for interdisciplinary collaboration


Approximate density-functional theory
Performance for biomolecular structures
Member of super-family of GPCR activation of
cellular pathways ? external signals
Density-Functional-based Tight-Binding DFTB
Reliable modelling of protein relevant bonding
interaction, inclus. solution
Additional inclusion of van der Waals bonding by
London dispersion formula
Elstner et al. PRB 1998, Frauenheim et al.
Phys.Stat.Sol. Jan. 2001 J Phys. C Jan 2002
Linear scaling method efficient QM-calculations
for reaction centers
QM/MM coupling for solution and environment
Crambin 2400 H2O
Solution of Kohn-Sham-equation using optimized
minimal basis including self-consistency in
Mulliken-charge distribution
Crambin (639)
W.Yang _at_ Duke
Comparable accuracy as ab initio at efficiency of
semiempirical methods all
interaction integrals from DFT ? high chemical
transferability
Retinal upon ultrafast photoisomerization now
activates the protein signaling state binding to
G-protein ? visual cascade
configurational changes of the chromophore ? confo
rmational changes of the protein
Handshaking with broad spectrum of experimental
data, including vibrational, optical, electron
spin and magnetic resonance spectra
Parallel 24-node SP2 Speedup factor 1000
M.Karplus _at_ Harvard
Project Overview
Major Expertise of the Research Group
Budgetary Details
Methpds all computational approachesrepresented
Collaboration with theory K.Schulten,
A.Warshel, M.Garavelli, W.Yang, M.Karplus,
M.Robb, J.Baudry, M.Olivucci
Collaboration with experiment G.Bueldt,
D.Oesterhelt, H.Martin, F.Siebert,
A.Der, H.Kandory, G.Zaccai, J.Lutgenburg,
K.Nakanishi, M.Sheves, S. Ruhman,
Biomolecular expertise of groups actively working
on retinal protein action