Xavier de Hatten
PhD Student in Organic Chemistry
University of Heidelberg, Germany
(co-supervised with Prof. Jeremy Smith)
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Xavier de Hatten PhD Student in Organic Chemistry University of Heidelberg, Germany (co-supervised with Prof. Jeremy Smith) |
| Project: Towards Synthetic Hydrogenase Mimicry: Force-Field Development and Molecular Dynamics Simulations of Novel-Synthesized Ferrocene-Bearing Peptides |
Model of the active site
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Abstract:
Hydrogenases,
found in numerous microorganisms, are of particular interest in the
field of
new energy research, because they catalyze the reversible conversion of
hydrogen into protons and electrons and thus have a potential
application in
hydrogen-based energy generation. Although
biological systems contribute at present
very little to the current energy production, they are capable of very
large-scale effects.
The increasing importance of hydrogenases in
the new energy research field has led
us to study the structure and dynamics of potential mimics, based on a
ferrocene-peptide scaffold, by means of Molecular Dynamics simulations.
As a
necessary first step towards realistic modelling of these compounds we
have
developed a new molecular mechanics force field for ferrocene-bearing
peptides
and implemented it in CHARMM. The ferrocene-bearing peptide thus
parameterized was ferrocene-1-(L)alanine-1’-(L)proline
and the resulting parameter set can be used for studying the molecular
dynamics
of all ferrocene-bearing peptides. The force field obtained was
subsequently
tested on independent experimental X-ray crystal structures. Simulations
performed in explicit dichloromethane solvent were also in good
agreement with experimental NMR and circular dichroism data. The force
field
developed was subsequently used to perform Molecular Dynamics
simulations on novel-synthesized ferrocene‑bearing peptides that mimic
the active site of Hydrogenase. Molecular Dynamics provides new
insights for
the synthesis of these compounds and possible reasons as to why
incorporation
of nickel in the hydrogenase active site has been unsuccessful up to
now.
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Jens Keienburg MSc Student in Molecular Biotechnology University of Heidelberg, Germany (co-supervised with Dr. Nicoleta Bondar) |
| Project: Force Field Development and Modeling of the Lipids and Bacteriorhodopsin in the Purple Membrane |
Bacteriorhodopsin + lipids top view
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Abstract:
The purple membrane is a two-dimensional crystalline lattice formed by
bacteriorhodopsin and lipid molecules in the cytoplasmic membrane of Halobacterium Salinarum. Many
high-resolution structural studies, in conjuction with detailed
knowledge of the lipid composition, make the purple membrane one of the
best possible models for elucidating the forces that are responsible
for the assembly and stability of integral membrane protein complexes.
Interactions between transmembrane helices of neighboring
bacteriorhodopsin (BR) molecules contribute to purple membrane
assembly. However, it has been postulated that other specific
interactions, particularly between BR and surrounding lipid molecules,
may provide the major driving force for assembly.
Using Molecular Dynamics simulations it is possible to interpret experimental results on complex membrane systems in details and to gain insight into the relevant interactions at the atomic level. As a necessary first step towards realistic modelling of these compounds we are developing a new molecular mechanics force field for the lipids with which BR is associated in the purple membrane. The major lipids of the Halobacterium Salinarum consist of the apolar moiety sn-2,3diphytanylglycerol (archaeol) attached to polar headgroups, which are not found normally in eukaryotic cells (sulfoglycolipids). Squalene is the major apolar lipid of the purple membrane other than the retinal. The force field developed will be subsequently used to perform Molecular Dynamics simulations on a model of the purple membrane, which will include one or more BR proteins and the essential lipids. The role of the BR-lipid interactions in the lattice assembly will be addressed. Relevant questions concern how the lipids bind to the protein and why it is critical for lattice assembly. Elucidation of the molecular basis of protein-protein and protein-lipid interaction in the purple membrane may provide insights into the formation of integral membrane protein complexes in other systems. |
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