New likelihood-based phasing methods in Phaser
Randy J. Read, Airlie J. McCoy, Laurent C. Storoni · Acta Crystallographica Section A Foundations of Crystallography · 2005
We have been developing a new program, Phaser, to apply likelihood to solving macromolecular crystal structures by molecular replacement and experimental phasing methods.Initial experiences with molecular replacement using brute-force likelihood targets in the program Beast [1] showed that likelihood had greater power to discriminate correct solutions, but the brute-force approach was prohibitively slow.To address this problem we have developed likelihood-based fast rotation [2] and fast translation [3] functions.The combination of these fast targets in Phaser with powerful automation strategies makes it possible to solve many difficult molecular replacement problems routinely.More recent developments in Phaser focus on experimental phasing.The program includes new likelihood targets for phasing by SAD [4], as well as by MAD or MIRAS (unpublished).Completion of the heavy-atom substructure is accomplished through the automated interpretation of log-likelihood-gradient maps.Applications of Phaser to difficult structure solutions will be discussed, along with plans for future development.