Building-block approach for determining low-frequency normal modes of macromolecules

Normal mode analysis of proteins of various sizes, ranging from 46 (crambin ) up to 858 residues (dimeric citrate synthase) were performed, by using st andard approaches, as well as a recently proposed method that rests on the hypothesis that low-frequency normal modes of proteins can be described as pure rigid-body motions of blocks of consecutive amino-acid residues. Such a hypothesis is strongly supported by our results, because we show that the latter method, named RTB, yields very accurate approximations for the low- frequency normal modes of all proteins considered. Moreover, the quality of the normal modes thus obtained depends very little on the way the polypept idic chain is split into blocks, Noteworthy, with six aminoacids per block, the normal modes are almost as accurate as with a single amino-acid per bl ock. In this case, for a protein of n residues and N atoms, the RTB method requires the diagonalization of an n x n matrix, whereas standard procedure s require the diagonalization of a 3N x 3N matrix. Being a fast method, our approach can be useful for normal mode analyses of large systems, paving t he way for further developments and applications in contexts for which the normal modes are needed frequently, as for example during molecular dynamic s calculations. Proteins 2000;41:1-7. (C) 2000 Wiley-Liss, Inc.