The revenge of the Patterson methods. I. Proteinab initiophasing

Abstract

Direct methods combined with direct-space refinement procedures are the standard tools forab initiocrystal structure solution of macromoleculesviadiffraction data collected up to atomic or quasi-atomic resolution. An entirely direct-space approach is described here: it includes an automated Patterson deconvolution method, based on the minimum superposition function, followed by an effective direct-space refinement, consisting of cycles of electron density modification. The new approach has been implemented in a new version of theSIR2004program and tested on a large set of test structures selected from the Protein Data Bank, with data resolution better than 1.6 Å and number of non-hydrogen atoms in the asymmetric unit up to 2000. The new procedure proved to be extremely efficient and very fast in solving crystal structures with atomic resolution data and heavy atoms: their solution and refinement requires a computing time roughly comparable with that necessary for solving small-molecule crystal structuresviaa modern computer program. It markedly overcomes direct methods, even for crystal structures with atomic data resolution and heaviest atomic species up to calcium, as well as for crystal structures with quasi-atomic data resolution (i.e.1.2–1.6 Å). The Patterson approach proved to be loosely dependent on the structure complexity.