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.


Hardware

Continuously updating local workstations.

NCHC (National Center for High-Performance Computing, HsinChu, TW)

NYMU cluster