Last month Birte Höcker, an experimental and theoretical protein scientist form the Max Planck Institute for Developmental Biology published an interesting article in Nature Chemical Biology. The general challenge described is that sequences that look different on first inspection can give rise to very similar 3D structures. It also shows a nice combination of bioinformatics complemented with experimental work. Central in this case are the two folds (Figure 1, blue and green):
- TIM barrel also known as the (βα)8-barrel consisting of 8 β-strands in the core and 8 α-helixes around
- Flavodoxin which folds with 2 α-helixes on the outside sandwiching 5 β–strands in the core.
So the common theme: they both have α–helixes on the outside, sheets on the inside.
The underlaying question here is: How is one fold converted to the other?
Last week I joined the International Synthetic and Systems Biology Summer School in Taormina, Italy and as the title describes it was all about Synthetic and Systems biology with some pretty cool speakers. Weiss talked about the general principles of genetic circuits and the current limitations (record is currently 12 different synthetic promoters in 1 designed network). Sarpeshkar focused on the stochastic nature and the associated noise of cells, he showed how they can be simulated or mirrored using analog circuits. Paul Freemont took Ron Weiss’ design principles and showed how to apply them on different examples, he also elaborated on an efficient way of characterizing new circuits and parts. Tanja Kortemme, a former postdoc from the Baker lab, gave an introduction to the capabilities of computational protein design and using some neat examples showed the power (and limitations) of computational design. Below some highlights and the relevant links of the literature that was discussed.
A selection of some interesting papers of the past period. Unfortunately some are only accessible for subscribers. Some topics covered; protein folding and design, antibiotic resistance genes, RNA polymerase complex and a paper on choosing the right color for your data.
Fig1: The Ubiquitin protein in cartoon representation used in the study (PDB: 1UBQ ).
Well this nanoscale torture rack is actually a sophisticated atomic force microscope (AFM) and the stretch is more ‘gentle’ then in the Medieval period, since it is (most of the time) reversible. The question arises; how can we describe these kind of extensions and can we, just as in basic material science, come up with an basic relationship between stress and strain?