Ferritin

Iron is the most abundant element on Earth by mass. Super-massive stars are able to fuse elements to higher and higher atomic weights as they evolve. They then die in supernova explosions and spew out their fusion products.  It happens that fusion up to the atomic weight of iron is heat generating but then heat absorbing after that, so it is not surprising that so much iron has accumulated in the universe. Iron is a transition element meaning that it has unfilled lower orbitals in its neutral state.  It can thus accept or surrender electrons with little change in its free energy which makes it ideal for mediating chemical reactions. It also makes it dangerous as it can readily react to whatever it bumps into.  Life, therefore from the very beginning has had to deal with it and the simple protein ferritin has been a universal answer, at least for the storage aspect. All life forms, prokaryotes, eukaryotes, and archaea have variants of ferritin.  Mitochondria and plastids even have their own variants.  The structure of all variants is highly conserved. 24 ferritin molecules interact to form a hollow ball. Iron ions in the +2 ferrous form are then deposited by ferritin inside the shell in the +3 ferric form (up to 4500 atoms per shell!), available for withdrawal as the need arises.

I have chosen ferritin as the ideal target of my folding software for several reasons.  It is relatively simple consisting of just four alpha helixes with a strap between them, and the many variants all have basically the same structure.  Hundreds of x-ray crystallization studies have been done on its many variants to high resolution including waters of hydration. Finally it interacts with  itself to form predictable macro structures. Mutant forms have even been generated and crystallized to provide insights on its folding and aggregation dynamics. It does, however, lack beta sheets so I will have to find another target eventually to fool around with.

New Title!

For the last few years, apart from minor revisions to the Protein Cycling Diet book, I have been playing around with the question of predicting how a polypeptide would fold if you knew only its amino acid sequence. This question is the holy grail of protein chemistry and has proven to be an exceedingly difficult problem and I hardly expect to solve it. I am now approaching it with a tool that I have not found others to have yet employed namely Jmol, an interactive viewer for three-dimensional chemical structures and a brilliant piece of work currently maintained by Bob Hanson of St. Olafs university.

I used to do my folding work in Java and then use Jmol to display the results. After Bob added the ability to edit polypeptides and in particular to rotate bonds, I was able to do all my work with the Jmol scripting language.  My initial output was a library of Jmol scripts: a set of tools for generating and manipulating polypeptides (and polynucleotides) found here. Now I am attempting to write scripts for predictive folding and have decided to discuss my project in this blog. Accordingly I have changed the title to the more general topic, Protein folding. After all, the earlier diet topic was about how to help dispose of misfolded proteins, so I have only broadened the scope of the blog and will continue to speculate here on relevant developments in autophagy science as well.