Rapid automated molecular replacement by evolutionary search

Abstract

A new procedure for molecular replacement is presented in which an efficient six-dimensional search is carried out using an evolutionary optimization algorithm. In this procedure, a population of initially random molecular-replacement solutions is iteratively optimized with respect to the correlation coefficient between observed and calculated structure factors. The sensitivity and reliability of the method is enhanced by uniform sampling of the rotational-search space and the use of continuously variable rotational and translational parameters. The process is several orders of magnitude faster than a systematic six-dimensional search, and comparisons show that it can identify solutions using significantly less accurate or less complete search models than is possible with two existing molecular-replacement methods. A program incorporating the method, EPMR, allows the rapid and highly automated solution of molecular-replacement problems involving single or multiple molecules in the asymmetric unit. EPMR has been used to solve a number of difficult molecular-replacement problems.