A stochastic approach to molecular replacement.

Abstract

The classical approach to the problem of placing n copies of a search model in the asymmetric unit of a target crystal structure is to divide this 6n-dimensional optimization problem into a succession of three-dimensional searches (rotation-function followed by translation-function searches for each of the models). Here, it is shown that a structure-determination method based on a reverse Monte Carlo minimization of a suitably chosen statistic in the 6n-dimensional space defined by the rotational and translational parameters of the n molecules is both feasible and practical, at least for small n. Because all parameters of all molecules are determined simultaneously, this algorithm is expected to improve the signal-to-noise ratio in difficult cases involving high crystallographic/non-crystallographic symmetry in tightly packed crystal forms. Preliminary results from the application of this method (obtained with a space-group general computer program which has been developed for this purpose) are presented.