Crystallographic ab initio protein structure solution below atomic resolution

Ab initio macromolecular phasing has been so far limited to small proteins diffracting at atomic resolution (beyond 1.2 angstrom) unless heavy atoms are present. We describe a general ab initio phasing method for 2 angstrom data, based on combination of localizing model fragments such as small alpha-helices with Phaser and density modification with SHELXE. We implemented this approach in the program Arcimboldo to solve a 222-amino-acid structure at 1.95 angstrom.