ABSTRACT
Throughout most of this book, protein domains are treated as being rigid and “tool-like.” And indeed for many purposes, this treatment is perfectly adequate. However, in reality proteins are not rigid: they have internal motions on a wide range of timescales and distance scales (Figure 6.1). This has a number of consequences for the way in which proteins work. The biggest aspect that this affects is enzyme activity. We have already seen the induced-fit model, which requires internal mobility. In this chapter, we see that conformational selection (or some balance between the two) is an even better model. A related area is protein:protein interactions, which again are not rigid-body interactions; they require mutual readjustment of the two partners. In many cases, internal mobility is helped by the presence of buried waters, which confer additional flexibility. The theoretical underpinning to much of this is the so-called “new view” of proteins, which sees proteins as a population of conformers, some of which can have structures quite different from the average, and which sees change between conformations not as a simple pathway between two states but as a change in populations. The consequences of these ideas are still being worked through in current research, both experimentally and theoretically, making the subject of this chapter an actively developing field (more than any other in this book except perhaps Chapter 9).
