Prof. Dr. Grubmüller showed the primary steps in photosynthesis, a process that charges the battery in plants by an excess of protons in a closed cycle.
Another example of bioinformatics simulation is the synthesizing of ATP. Everything which consumes in the human body uses ATP.
Proteins are not small molecules. Proteins are far more complex than a water droplet structure or a salt crystal.
There is a huge diversity in proteins according to their function, explained Prof. Dr. Grubmüller. Protein structures are being stored in the Protein Data Bank to study their function.
Aquaporins are perfect water filters. In fact it are water channels. Scientists wonder how strong the water molecules bind to their neighbours. Some of them have to be broken to get rid of the neighbours and to brake the bonds. We are talking discrepancy of one million fold here. Researchers have to set up a simulation system to study the binding.
Prof. Dr. Grubmüller presented the simulation of water transport. About 100.000 atoms are in the game with full electrostatics and periodic boundary for 10 nanoseconds of simulation time. Atoms change their velocity and they move over a distance which changes their structure. Water permeation proceeds in steps. One out of 16 full spontaneous permeastion events of about 2 nanoseconds was being displayed.
To study the water pathway and hydrogen bonding in Aquaporin-1, researchers need timescales of protein motions. Biochemistry deals with the grating of channels; the enzymatic reactions; the molecular motors; and the recognition. This simulation process needs TeraFlop today, noted Prof. Dr. Grubmüller. Researchers try to accelerate the processes but not to change the nature of the process, just make it faster.
Single molecule force spectroscopy is used in a streptavidin/Biotin unbinding simulation. Titin is a giant muscle protein: 3000 kDa or ca. 400g of body weight. Titins are rubber band to prevent the whole muscle machine to collapse due to overstretching.
Why is there a titin kinase? Why is there a force sensor? If you pull at two sides, you expose the spinal side. The sample force probe MD simulation is showing an asymmetric rupture of beta sheets. The scientific prediction is an exposure of the binding site, with ATP.
The pulling simulation is set up to see how the body works. In the F-ATP Synthase, Prof. Dr. Grubmüller is asking where the energy is. It is not in the proton, not in the ATP. The elastic properties of the F1-ATPase rotor can be studied in the simulation set-up measuring the elasticity.
Another simulation example is that of the fluctuating gamma subunit. Here the action of the machine is being simulated. It behaves almost like an auto-engine. First there are the conformational changes, then the binding change mechanism or ATP synthesis, followed by the simulation of the rotation.
The timing and sequence of conformational changes in B ATP looks like a kind of falling-domino-stones structure in transmitting the energy.
Then Prof. Dr. Grubmüller showed a world record: the mechanical properties of the Southern Bean Mosaic Virus. The pressure inside goes up to 50 atm which is a very high pressure. These are fully atomistic simulations in an AFM experiment with force probe simulation.
There is a deformation during the indentation. Researchers use the simulation to colour the elastic constants.
Prof. Dr. Grubmüller ended by describing the future work, consisting in the study of the anatomy of a synaptic vesicle in the brain. Can we also identify and classify dynamics motifs, he was asking. Life processes can be understood from the jiggling and giggling of molecules, according to Richard Feynman. And this is exactly what molecular dynamics is doing: calculating the jiggling and giggling of molecules.