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Modelling Viral Channel Proteins
Molecular self assembly:
Molecular self-assembly is one of the techniques which is used by
nature to compose almost all living matter. In its extreme cases,
molecular self-assembly covers the range of modulator binding up to the
large scale 2D assembly of membrane proteins within the lipid bilayer
e.g. during the budding process. We investigate the conformation space
of a series of viral channel and pore forming proteins, such as Vpu
from HIV-1, 3a from SARS-CoV and p7 from HCV. The
exact number of assembling proteins forming the homo oligomeric bundles
is unknown. Thus, computer simulations play an important role to (i)
explore pathways for protein approach and (ii) finally to predict
protein-protein interactions until further experimental evidence is
available.
Diffusion of ions and substrates:
The proper simulation allows us to monitor the reliability of the
protein assembly and to derive protocols for ligand diffusion, thereby
supporting modulator development for bionanotechnology. Currently we
are using steered molecular dynamics (MD) simulations. With steered MD
an additional directional force is applied to specific parts of a
molecule at each time step during the simulation. This protocol allows
to model the flux of ions and substrates into narrow pore geometries
based on a Langevin equation and to derive an estimate of the free
energy profile along the reaction coordinate. In this respect we
developed novel computational protocol for calculating more accurately
kinetic data for modulator - protein interactions. Currently
conductance measurements are used for the characterization of
especially channel forming proteins.
Protein folding:
For only a few viral membrane proteins experimentally derived structural
information is available. With the rapidly increasing number of viral
proteins discovered to be located within or attached to the membrane
computational tools become a valuable tool to predict the fold of these
proteins. We aim to develop computational methods that enhance the accuracy
of the prediction. The concepts of folding will also be adapted to describe
the mode of action of these proteins.
Hydrogen bonding:
The mechanism of function of proeins is amongst other forces driven by hydrogen bonding. On a cellular level changes of hydrogen bonding pattern is an effective tool to steer the cellular life cycle. The role of hydrogen bonding in terms of singular as well as in collective events during protein mechanics and ligand binding is investigated. We elaborate on simulation techniques which allow to include characteristecs of hydrogen bonding.
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