Section 20.2.6. Internal dynamics and average structures

It is most often the goal of the structural biologist to define a single average structure of a macromolecule. The well recognized internal motions arising from thermal fluctuations of a macromolecule may be necessary for function, but, nonetheless, the methods of structure determination generally aim to model a single average structure. Internal motions range from the high frequency, small amplitude motions (i.e. those modelled by crystallographic B values) to low frequency, larger amplitude motions of loops and whole domains. Some studies (Kuriyan et al., 1986; Post, 1992) have examined the validity of the assumptions about fast timescale motions made by the methods of structure determination. It is reasonable that some of the differences between the structure solutions of a protein obtained by NMR spectroscopy and X-ray crystallography are due to differences in the effects of internal motions. The application of molecular-dynamics algorithms for structure determination has allowed the use of protocols that account for effects of internal motions by employing time-averaged restraints (Schiffer et al., 1995).