Panel Discussion: How Rigid are Proteins and Do We Care?

Abstract

I guess the title of this is ”Protein flexibility, so what?” Actually that may be a meaningful way of putting it, because I think you can certainly talk to some groups for whom the concept that proteins are flexible things is a revelation and you can also talk to other groups, for example, many physical chemists who say, well, we knew these things were at room temperature and therefore they had to move and so why are you telling us anything. One of the questions in this conference is the role of flexibility in chemical reactivity. Presumably some problems in chemical reactivity have to do with very fast processes, but the processes that are presumably of physiological significance are ones which are relatively slow on the time scale of molecular dynamics. In any event, things on the microsecond to millisecond time scale, and for these processes, it has certainly become clear that flexibility of the protein is important, if the protein was an absolutely rigid structure, for example, oxygen would never get in, that was shown by the case in Karplus’ studies, however, it’s not so clear yet whether the dynamics of this flexibility is important or not because most of the studies we’ve seen have been of processes much, much faster than these microsecond/millisecond events. Still, these rapid processes are important to study because they certainly modulate the time dependence on the longer time scales and they also tell us what the actually equilibrium state is. Many of the things that we’re interested in are just what does the protein look like, how is information stored in it. So I think that in many cases, the studies that we’re doing dynamically are just trying to act as a probe of equilibrium structure and we’re doing dynamics because we don’t know how to do anything better. We don’t have x-ray microscopes.