Protein Crystallization Hits

There's so much progress in membrane protein crystallography generally, and in GPCR crystallography in particular, that I've started a new blog, called GPCR blog. I'm planning to cover topics relating to GPCR structural biology via the Emerald BioStructures website (note the URL: http://emeraldbiostructures.com/gpcrblog). For anybody who's interested in experimental GPCR crystallization conditions, these blog posts may be interesting to read: GPCR Crystallization Conditions  and GPCRs of known structure.

This is a good opportunity to attempt a quick look into the future and anticipate what's yet to come in our field. It is indeed amazing to see all the progress that's been made in the field of membrane protein research within the past ten years. When I decided to join the membrane protein structure research field - this was around the mid nineties - I was warned that this is a super high risk field, may derail my dreams of getting a PostDoc position and not land me a job in either academia or industry. And now, years later, there are so many more crystallographic membrane protein structures - getting close to hundred (depending how you count) and there are substantial efforts in the pharma and biotechnology industry to apply these difficult targets to crystallography based ligand discovery and to lead optimization in drug discovery programs. This is similar to what happened in the late 80ies to soluble protein structure research. Our game has changed dramatically since then, hasn't it?

It feels like a time warp looking at all the progress made in membrane protein structural biology.

So, what's next?

To me the next big steps in structural biology are about scale context in time and space. What does that mean?

1. A better understanding (with atomic resolution, of course) of the detailed dynamics within protein molecules as they go about their work. More precisely, an experimental understanding of how the motions of atoms and their bond rotations & translations taking place in the sub-nanosecond timescale create effects that manifest themselves in what we call "biochemical function" at the milli to second timescale (6-9 orders of magnitude scale difference).
2. The integration of structural data from atoms up, to explain the appearance of macroscopic structures such as cells and organisms (again ca. 6 orders of magnitude).

Of course both of these fields rely heavily on computational tools and require a lot of input by experimentalists as well, providing reality checks and help keeping the models grow better.

My 2 ct,
Peter