Ab initio phasing of a 4189-atom protein structure at 1.2 A resolution

The phase problem remains a key rate-limiting step in the determination of macromolecular X-ray structures. Direct methods, applying probability theory to the native data set, can routinely solve structures of up to about 200 non-H atoms, although much larger structures have been solved given sufficiently high resolution data and the presence of heavy atoms. Here it is shown that maximum-likelihood refinement of free-atom models with ARP/wARP can solve ab initio a much larger metalloprotein structure than the largest so far solved by conventional direct methods. The protein, OppA, is not naturally associated with metal ions but was co-crystallized with uranium.