Hi, I've been looking around a bit to try to find a description of this job with no luck. Does anyone know what all these HetTest1_ChainA_HestTest1_ChainB jobs are looking at???

(I've gotten a number of them recently, they look like really complex structures in the screensaver - more so then anything I've seen for a while, and it's peaked my interest)

Hi Timo,

I alerted the scientist that submitted these jobs! He'll provide some details soon! =]

Hi Timo,

First of all, thanks all for your contribution and sorry for the delayed answer. Here is a description of the project:

One of the paradigms in protein design is the design of novel protein-protein interactions, this is the basis of molecular recognition in living organisms and an important milestones yet to be attained by human-designed proteins. Different kinds of protein-protein interactions happen all the time on living organisms. A common well-known example that highlights the importance of protein-protein recognition is the specific interaction that happens during human immune response where neutralizing antibodies recognize proteins from pathogens, leading to the inactivation and eventual clearing of the pathogen. The design of protein-protein interactions is not a trivial task and recently we have started a project that combines the design of novel proteins and the task of mastering the design protein-protein interactions, with the aim to create novel protein heterodimers (i.e. two different proteins interacting specifically,for a previous example of this kind of design but using as starting point natural-existing proteins see http://www.bakerlab.org/node/353/), by doing this we aim to gain the ability of constructing molecular switches that eventually permit the creation of more complex functions, for example enzymatic reactions that take place only when two specific-proteins are present, namely a molecular switch. In order to do this we start by using a database of novel protein structures which have been designed and experimentally corroborated by our group (mainly form: http://www.bakerlab.org/node/465/ and http://www.bakerlab.org/node/82/), then we use an exhaustive sampling algorithm to generate thousands of plausible combinations of pairs of these proteins that hold the potential of attain geometric complementarity (think about a key and a lock), however these proteins weren't originally designed to interact between them (and they don't), henceforth we use computational methods to design molecular complementarity between them, this is to create a novel protein-protein interface. By using this general method, we design thousands of potential pairs of unique proteins that have the potential to form a stable heterodimer. After multiple rounds of design and selection, we still have hundreds of combinations that are potential candidates for experimental testing. It is at this stage that we finally use our most powerful computational resource (Rosetta@Home) to validate and select the best designs among the pool. Here is where the contribution of donor’s computational time (like you, thanks!) becomes a crucial part of our project. It is at this last computational stage of the design process that we combine two computational-intensive strategies to verify and select our best designs. First is the verification of the protein's sequences to attain/fold-into the desired three-dimensional structure (namely, forward folding), and the second is to test the ability of a given pair of proteins (that succeed in the previous stage) to form in an specific heterodimer-interaction (namely, ab-initio docking), the former is the type of computation that you are enquiring in this post. A great explanation about the aim and inner-workings of the docking calculation has been previously provided by Chu Wang in this forum (see https://boinc.bakerlab.org/rosetta/forum_thread.php?id=2395#29146).
Currently we are running 333 ab-initio docking simulations for our candidate heterodimers, all of them will be finished soon. Using the results of these calculations we will select for experimental validation only the best candidates that succeed in the aforementioned computational tests.
As this project progress I'll keep posting regular updates in this forum..
Once more, thanks to all the donors for their invaluable contribution to R@H.

Daniel-Adriano Silva

Amazingly detailed explanation. Thank you so much!