I just returned from the American Chemical Society conference in Philadelphia. This was my first experience at ACS and I attended several computational chemistry symposium. There is still much for me to learn about computational chemistry but I feel that this project is on the right research track in its development with integrating docking and molecular dynamics simulations. Understanding how to apply these tools for problems relevant to biological hydrogen production is challenging. Our strategy has been building models for proton reduction catalyzed by Fe-Hydrogenase using an open source MD and finding ways to create custom force field parameters. I see now how to do this conceptually, but there are problems with this approach. There is not enough empircal data to use for these models. The structures of the iron prosthetic groups are not fully understood so this makes it challenging to predict reaction mechanisms. If we could predict the reaction mechanism, then it should be possible to design or find alternative enzymes to Fe-Hydrogenase.

Since the problem with biological water splitting hydrogen production is the interaction between evolving oxygen molecules and Fe-Hydrogenase, another approach is keeping Oxygen away from Fe-Hydrogenase. Now how can we do that? Introduce a molecule that has a higher affinity for oxygen than Fe-Hydrogenase. Once attached, this molecule will safely float away and transport the Oxygen out the cell. Where on earth would anyone find molecule like this? Every hear of Hemoglobin? Hemoglobin transports oxygen from lungs to cells in many animal species. Whether the biochemistry of Hemoglobin is compatible with plant species is an unknown, maybe we can study the properties of hemoglobin to find similar proteins. Dock oxygen molecules to these hemoglobins, then run classical md to see how they transport through the algae. Finally, we want to know whether the protein will release the the oxygen molecules, we may be able to model this with a semi-empirical QM/MM if we can get a good description of the environment near the algea's cell wall.
-Jack