Oligomerization, diseases, and Folding@home

[Jesse_V]

I'm trying to understand what oligomerization is, its implications into disease, and how Folding@home is helping. I've heard that it creates a relatively ordered structure, in contrast to aggregation which is very disordered and thus difficult to experimentally examine. Oligomers apparently consist of a few monomer units, so its basically like a polymer except that there are very limited number of monomers. I think I have a very general understanding of protein misfolding and aggregation and their roles in diseases, but oligomerization is very new to me and I've heard very little about it. Can someone explain or refer me to a good explanation?

Folding@home seems to tackle biomedical molecular problems which are 1) have roles in diseases or would help with cures/drugs, 2) are experimentally difficult to study in detail, and 3) where straightforward simulations run into major difficulties when tackling it. I would assume oligomerization is the same way. I also know that amyloid beta oligomerization appears to be toxic, and together with aggregation causes Alzheimer's. Folding@home has also address p53 oligomerization as part of cancer research. I know that the Pande lab focuses primarily on science and not touring this forum, but I'm hoping that there's someone here who knows something about this process and who has the time to some information into the three aspects I have outlined above. I'm intent on learning about it, and I'm curious how its such a difficult thing to examine when its apparently much more orderly than aggregation. Can anyone explain please?
Thank you for your time.

[VijayPande]

Misfolding is often combined with oligomerization. That's the case in AD for example, where Aß peptides oligomerize and it's now believed by many (most?) researchers that it is the oligomeric (not fibril) forms are the true toxic element in AD.

[Jesse_V]

Misfolding is often combined with oligomerization. That's the case in AD for example, where Aß peptides oligomerize and it's now believed by many (most?) researchers that it is the oligomeric (not fibril) forms are the true toxic element in AD.

Ah thanks! I've heard about the connection with oligomerization and AD, interesting that the connection is so widely believed. Could you please elaborate a bit more on what exactly it is, its implications into disease, and why its so difficult to study? I've also heard about p53 oligomerization as well, and you guys produced a paper in 2004 which you've said was the first cancer-related publication from a DC project. I'm just new to it but I'd like to understand. I appreciate you taking the time to respond here already.