Section 25.2.10.3.2. Integrated Patterson and direct methods: SHELXD

The program SHELXD (Sheldrick & Gould, 1995; Sheldrick, 1997, 1998b) is now part of the SHELX system. It is designed both for the ab initio solution of macromolecular structures from atomic resolution native data alone and for the location of heavy-atom sites from ΔF or F_A values at much lower resolution, in particular for the location of larger numbers of anomalous scatterers from MAD data. The dual-space approach of SHELXD was inspired by the Shake and Bake philosophy of Miller et al. (1993, 1994) but differs in many details, in particular in the extensive use it makes of the Patterson function that proves very effective in applications involving ΔF or F_A data. The ab initio applications of SHELXD have been described in Chapter 16.1 , so only the location of heavy atoms will be described here. An advantage of the Patterson function is that it provides a good noise filter for the ΔF or F_A data: negative regions of the Patterson function can simply be ignored. On the other hand, the direct-methods approach is efficient at handling a large number of sites, whereas the number of Patterson peaks to analyse increases with the square of the number of atoms. Thus, for reasons of efficiency, the Patterson function is employed at two stages in SHELXD: at the beginning to obtain starting atom positions (otherwise random starting atoms would be employed) and at the end, in the form of the triangular table described above, to recognize which atoms are correct. In between, several cycles of real/reciprocal space alternation are employed as in the ab initio structure solution, alternating between tangent refinement, E-map calculation and peak search, and possibly random omit maps, in which a specified fraction of the potential atoms are left out at random.