More Fun with Catalysts

[DrLemming]

Widespread use of clean-burning hydrogen for fuel would be an amazing step forward for society. Have we mentioned recently how amazing? Oh that’s right, we have.

https://fold.it/portal/node/994490

To recap: molecular hydrogen (H2) produces water when it’s burned, and can be re-made from water plus a bit of energy. Well, a LOT of energy, but that’s where hydrogenase catalysts come in: if we can reduce the cost of producing hydrogen from water, we can power everything with clean, near-unlimited hydrogen that we can make cheaply at our power plants or in-home plug-in hydrogen makers. If we get a good enough hydrogenase catalyst working, the future becomes really exciting.

We’ve shown you a hydrogenase catalyst before (Puzzle 644: http://fold.it/portal/node/993779 ). Now we’ll be working with a different catalyst with proven activity; a nickel-phosphine dimer inspired by the active sites of some natural enzymes. We can watch hydrogen bubble off it when we apply a small current to feed it electrons. This catalyst was developed at PNNL (Pacific Northwest National Labs, in south-central Washington State) by a group led by Daniel DuBois. It’s a really neat molecule, and more information can be found at the PNNL website here: http://www.pnl.gov/news/release.aspx?id=883

The good news is that we’ve already proven we can attach peptides to this catalyst without making it worse. (This is a bigger hurdle than you might realize!) With peptide attachments –specifically, with YOUR help building good peptide attachments – we can make this a much better catalyst.

So, how do we make this catalyst a game-changer? For starters, we’re just looking for interesting, compact designs. Just putting this catalyst into a protein-like environment and determining its structure would be a huge step forward. But this isn’t just about making our catalyst a cozy little apartment out of protein. We need to feed protons (hydrogen atoms) to the active site so we can assemble hydrogen faster.

We also need to hold the catalyst in place so that it can’t wiggle. The catalyst is more flexible than it appears in our puzzle. It can bend into other conformations where it stops working as a catalyst. But with a strong, compact protein support, we’ll be able to hold it in the working conformation so that it stays active more of the time.

Many natural enzymes do exactly this sort of thing: they encase their active site in a protein machine that keeps it stable, and “feed” it protons or other molecules it needs. If we can get a Borg-like hybrid protein/small-molecule catalyst working, we won’t just make a big step towards a hydrogen energy economy, we’ll also have a unique hybrid bio-machine to brag about. :)

Future puzzles will provide bonuses for reaching either the central metal or nearby nitrogen with polar hydrogen atoms. But for this first puzzle (#675: https://fold.it/portal/node/994490) just have fun building up peptide scaffolding to wrap around the catalyst.

Technical advice (for puzzle #675 and those like it):

Feel free to look to previous two-chain symmetric design puzzles for inspiration, but don’t limit yourself to what’s worked before, since this big central molecule linking your two chains provides new opportunities and new challenges. Specifically, the two chains are now permanently stuck together, so you don’t have to worry about two separate chains finding each other; they count as one chain now, so they don’t have to be able to fold up on their own. On the other hand, the bulky molecule in the middle means that the available geometries for packing the chains are more limited, and to get a good score you’ll probably have to include at least part of that big molecule in your core.

Even more technical: be warned that it’s going to be trickier than normal to wiggle and rebuild segments near the N-termini of the two chains, since they’re locked together at the catalyst.

[steveB]

Hi,

Would it be possible for you to upload a larger foldit graphic of the catalyst, preferably a screen shot taken directly from puzzle 675, with the atoms labelled - which is the Nickel, Nitrogen etc ?

At present we have the PNNL graphic, the foldit graphic in this article which has white,black and blue pieces, and the in-game graphic which is grey with two red 'acceptor' atoms near the catalyst core, and I am relatively confused as to what is what.

Thanks

[DrLemming]

Here's a better view of the catalyst from the puzzle, in all-atom (stick+H) view mode, with the important atoms labeled. (Note: there are two nitrogens per catalyst, four phosphorus atoms, and one nickel at the very center of symmetry. The carbon, hydrogen, and phosphorus atoms don't do much besides keep the molecule together.)
catalyst; atoms labeled: (not labeled: lots of less-important carbon and hydrogen atoms.)

A run-down on why the atoms are the colors they are, in Foldit:
The nitrogen atoms will show up as red acceptors when "show bondable atoms" is checked (because this view option colors atoms based on whether they want to donate protons - blue - , accept protons - red -, or both - purple.)
But if you look at nitrogen atoms in Score/Hydro+DPK mode they appear blue (because this view option colors atoms based on what element they are: nitrogen is blue, hydrogen is white, oxygen is red, phosphorus is cream, nickel is black, and carbon is the "base" color: orange or cyan for sidechains but varies depending on residue energies for the backbone. For this catalyst, we had to convert a carbon atom into a "virtual" atom to avoid clashes between the catalyst and peptide, so there's a carbon atom at the bottom left of the image that appears black.) The Score/Hydro+CPK and stick+H view options only show up in the view menu when "advanced GUI" is enabled, so it's not intuitive.

One last thing: this catalyst technically switches between the nitrogen being a proton donor and being a proton acceptor - in fact, that's precisely why it's a good catalyst. :) We've given you the "proton acceptor" version because putting protons back onto that nitrogen is the rate-limiting step; it's what's currently holding this catalyst back. Getting H-bond donors near the nitrogen (in its "proton acceptor" form) should help speed it up!

[steveB]

Thanks for the very helpful information and clarification of the colour system used in foldit.