Analysis of domain motions in large proteins

We present a new approach for determining dynamical domains in large protei ns, either based on a comparison of different experimental structures, or o n a simplified normal mode calculation for a single conformation. In a firs t step, a deformation measure is evaluated for all residues in the protein; a high deformation indicates highly flexible interdomain regions. The suff iciently rigid parts of the protein are then classified into rigid domains and low-deformation interdomain regions on the basis of their global motion . We demonstrate the techniques on three proteins: citrate synthase, which has been the subject of earlier domain analyses, HIV-1 reverse transcriptas e, which has a rather complex domain structure, and aspartate transcarbamyl ase as an example of a very large protein. These examples show that the com parison of conformations and the normal mode analysis lead to essentially t he same domain identification, except for cases where the experimental conf ormations differ by the presence of a large ligand, such as a DNA strand. N ormal mode analysis has the advantage of requiring only one experimental st ructure and of providing a more detailed picture of domain movements, e.g. the splitting of domains into subdomains at higher frequencies. Proteins 19 99;34:369-382, (C) 1999 Wiley-Liss, Inc.