Folding Forum

Right now there are a lot of things that are easily manipulatable through recombinant technology but we dare not for feared consequences.

Right now there are human antibody libraries created by CDR shuffling that are pretty useful. I was wondering if there was any instance of folding at home studying a hypothetical protein's properties. For we can make the hypothetical protein through recombinant technology and It think FAH would be a much better way of seeing what should be persued iin terms of new vaccine development and therapeutic agents. For example (and it may be trivial I don't know) would an antibody with 7 CDRs as opposed to 6 bind effeciently? Can more efficiently binding molecules be found?

It's speculation but interesting speculation.

Cheers,
John

No, F@H does not do speculation. They are trying to understand real folding and misfolding, to find solutions for real diseases and disorders of protiens misfolding.

jheil wrote:I was wondering if there was any instance of folding at home studying a hypothetical protein's properties.

There are, but not in the context you mean. Many FAH projects use the synthetic construct BBA5 ( http://scop.mrc-lmb.cam.ac.uk/scop/data ... b.b.e.html ) as a substrate. These projects have been used for a variety of purposes including QA on new cores etc to make sure they are working correctly (BBA5 is a 23AA long protein whose folding process is well characterised). BBA5 is also used for projects that are more interested in how the environment affects folding rather than the folding process itself. Paper 18 (http://fah-web.stanford.edu/papers/rhee ... 04pnas.pdf) is such a case, where the aim was to study the effect of solvent (water) on the folding system.
BBA5 was also the protein used in the comparison between in vitro and in silico folding, see paper 8 (http://fah-web.stanford.edu/papers/SnowNature2002.pdf).

jheil wrote:For we can make the hypothetical protein through recombinant technology and It think FAH would be a much better way of seeing what should be persued iin terms of new vaccine development and therapeutic agents. For example (and it may be trivial I don't know) would an antibody with 7 CDRs as opposed to 6 bind effeciently? Can more efficiently binding molecules be found?

Some work has been done to this end, but not with hypothetical or designed proteins.
The techniques in Paper 43 (http://www.stanford.edu/group/pandegrou ... 084901.pdf) could conceivably be used to find more efficient binding molecules. In the paper the free energy of binding was calculated for 8 ligands of the FKBP12 protein which is not too dissimilar in concept to your antibody suggestion, you could potentially be screening a vast number of potentials molecules though.