By Ty Thomson
We all know that proteins aren't rigid structures. Proteins are constantly pulsing, wobbling, shifting conformations and generally not just sitting still. Despite this, it’s often much easier to think of them as rigid structures.
We also tend to think of allosteric activation as a shift from a single low activity structure to a single high activity structure. After all, these static inactive and active conformations are what we are so keen to identify in crystallography studies. However, in reality, proteins likely spend time in both low and high activity structures/conformations regardless of whether they have been allosterically “activated”; allosteric activation merely shifts the balance so the protein spends more time in the active conformation.
Although the rigid body approximation may simplify matters in our mind when thinking about problems, it’s always important to keep in mind the reality of the situation. Especially since the reality suggests that even inactive proteins probably spend some amount of time in their active conformation, and this can have very real biological implications. For example, it can lead to all kinds of basal activity in signaling pathways, and often the basal activity is important for proper pathway function.
There are many other reasons to consider the molecular dynamics of proteins. For a longer and more detailed discussion, read the article in a special Protein Dynamics issue of Nature that motivated this blog post (PubMed link). The article was a bit tough to read, but the ideas, although likely familiar to many researchers, are important to keep in mind and the article was a good refresher.
