Rapid automated molecular replacement by evolutionary search

A new procedure for molecular replacement is presented in which an efficien t six-dimensional search is carried out using an evolutionary optimization algorithm. In this procedure, a population of initially random molecular-re placement solutions is iteratively optimized with respect to the correlatio n coefficient between observed and calculated structure factors. The sensit ivity 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 raste r than a systematic six-dimensional search, and comparisons show that it ca n identify solutions using significantly less accurate or less complete sea rch models than is possible with two existing molecular-replacement methods . A program incorporating the method, EPMR, allows the rapid and highly aut omated solution of molecular-replacement problems involving single or multi ple molecules in the asymmetric unit. EPMR has been used to solve a number of difficult molecular-replacement problems.