Lively proteins move and shake
May 23, 2001
Proteins are much more dynamic structures than originally thought, according to biophysicists at the University of Pennsylvania in the US. In the most comprehensive study of its kind, Joshua Wand and Andrew Lee found that the side chains of long protein molecules shake rapidly with three distinct kinds of movement. The discovery could lead to the development of drugs that can more effectively target accessible sites on the protein (A Lee and A Wand Nature 2001 411 501).
Wand and Lee used nuclear magnetic resonance to probe the motion of the methyl-bearing side chains of the protein calmodulin, which regulates muscle contraction. They found that a single oscillation of a side chain takes less than a nanosecond but, more surprisingly, that the degree of movement is extremely varied and falls into three separate bands. Wand emphasizes that it is the ability of the side chains to oscillate in a variety of modes - or 'entropy' - that is remarkable.
The researchers observed the behaviour of the three classes of movement - semi-rigid, moderately mobile and moving freely - at a range of temperatures between 278 and 346 K. They discovered that the side chains became much more active as the temperature rose for all three modes of vibration. "Most people assume the internal entropy of protein is limited and unimportant", Wand told PhysicsWeb, "but we have shown that this is not true - it is large and potentially very important in biological processes".
Although they studied the dynamics of only one protein, the researchers believe that all proteins will behave in a similar fashion. The pair examined existing studies of other proteins, which were carried out at a single temperature, and found that the same three classes of motion were present.
Earlier crystallographic experiments revealed that proteins undergo a structural transition - from rigid to more fluid - at a certain temperature. This was dubbed a 'glass transition' by physicists, but Wand and Lee now believe that the transition arises from peaks in the lower and middle bands of motion rather than 'real' glassy behaviour. "The beauty of this study is that motion and temperature are inextricably linked", says Lee, "and this tells us more about the motion itself".