NEW APPROACH FOR DETERMINING LOW-FREQUENCY NORMAL-MODES IN MACROMOLECULES

A new method for calculating a set of low-frequency normal modes in ma cromolecules is proposed and applied to the case of proteins. In a fir st step, the protein chain is partitioned into blocks of one or more r esidues and the low-frequency modes are evaluated at a low-resolution level by combining the local translations and rotations of each block. In a second step, these low-resolution modes are perturbed by high-fr equency modes explicitly calculated in each block, thus leading to the exact low-frequency modes. The procedure is tested for three cases-de caalanine, icosaleucin, and crambin-using a perturbation-iteration sch eme in the second step. Convergence properties and numerical accuracy are assessed and tested for various partitions. The low-resolution mod es obtained in the first step are always found to be good starting app roximations. Potential advantages of the method include a central proc essing unit time roughly N-2 dependent on the size of the problem (N b eing the number of degrees of freedom), the possibility of using paral lel processing, the nonrequirement for loading the complete mass-weigh ted second-derivative input matrix into central memory, and the possib ility of introducing in the procedure further structural hierarchy, su ch as secondary structures or motifs. In addition, any improvement or refinement of the algorithm benefits from the efficient formalism of t he effective Hamiltonian theory. (C) 1994 John Wiley & Sons, Inc.