Tables for
Volume F
Crystallography of biological macromolecules
Edited by E. Arnold, D. M. Himmel and M. G. Rossmann

International Tables for Crystallography (2012). Vol. F, ch. 16.1, pp. 419-420   | 1 | 2 |

Section 16.1.8. Utilizing Pattersons for better starts

G. M. Sheldrick,a C. J. Gilmore,b H. A. Hauptman,c C. M. Weeks,c* R. Millerc and I. Usónd

aLehrstuhl für Strukturchemie, Georg-August-Universität Göttingen, Tammannstrasse 4, D-37077 Göttingen, Germany,bDepartment of Chemistry, University of Glasgow, Glasgow G12 8QQ, UK,cHauptman–Woodward Medical Research Institute, Inc., 700 Ellicott Street, Buffalo, NY 14203–1102, USA, and dInstitució Catalana de Recerca i Estudis Avançats at IBMB-CSIC, Barcelona Science Park. Baldiri Reixach 15, 08028 Barcelona, Spain
Correspondence e-mail:

16.1.8. Utilizing Pattersons for better starts

| top | pdf |

When slightly heavier atoms such as sulfur are present, it is possible to start recycling procedures from a set of atomic positions that are consistent with the Patterson function. For large structures, the vectors between such atoms will correspond to Patterson densities around or even below the noise level, so classical methods of locating the positions of these atoms unambiguously from the Patterson are unlikely to succeed. Nevertheless, the Patterson function can still be used to filter sets of starting atoms. This filter is currently implemented as follows in SHELXD. First, a sharpened Patterson function (Sheldrick et al., 1993[link]) is calculated, and the top 200 (for example) non-Harker peaks further than a given minimum distance from the origin are selected, in turn, as two-atom translation-search fragments, one such fragment being employed per solution attempt. For each of a large number of random translations, all unique Patterson vectors involving the two atoms and their symmetry equivalents are found and sorted in order of increasing Patterson density. The sum of the smallest third of these values is used as a figure of merit (PMF). Tests showed that although the globally highest PMF for a given two-atom search fragment may not correspond to correct atomic positions, nevertheless, by limiting the number of trials, some correct solutions may still be found. The two-atom vectors are chosen by biased random sampling that favours the vectors corresponding to higher Patterson values. The two atoms may be used to generate further atoms using a full Patterson superposition minimum function or a weighted difference synthesis.

In the case of the small protein BPTI (Schneider, 1998[link]), 15 300 attempts based on 100 different search vectors led to four final solutions with mean phase error less than 18°, although none of the globally highest PMF values for any of the search vectors corresponded to correct solutions. Table[link] shows the effect of using different two-atom search fragments for hirustasin, a previously unsolved 55-amino-acid protein containing five disulfide bridges first solved using SHELXD (Usón et al., 1999[link]). It is not clear why some search fragments perform so much better than others; surprisingly, one of the more effective search vectors deviates considerably (1.69 Å) from the nearest true S–S vector.

Table| top | pdf |
Overall success rates for full structure solution for hirustasin using different two-atom search vectors chosen from the Patterson peak list

Resolution (Å)Two-atom search fragmentsSolutions per 1000 attempts
1.2 Top 100 general Patterson peaks 86
1.2 Top 300 general Patterson peaks 38
1.2 One vector, error = 0.08 Å 14
1.2 One vector, error = 0.38 Å 41
1.2 One vector, error = 0.40 Å 219
1.2 One vector, error = 1.69 Å 51
1.4 Top 100 general Patterson peaks 10
1.5 Top 100 general Patterson peaks 4
1.5 One vector, error = 0.29 Å 61


Schneider, T. R. (1998). Personal communication.
Sheldrick, G. M., Dauter, Z., Wilson, K. S., Hope, H. & Sieker, L. C. (1993). The application of direct methods and Patterson interpretation to high-resolution native protein data. Acta Cryst. D49, 18–23.
Usón, I., Sheldrick, G. M., de La Fortelle, E., Bricogne, G., di Marco, S., Priestle, J. P., Grütter, M. G. & Mittl, P. R. E. (1999). The 1.2 Å crystal structure of hirustasin reveals the intrinsic flexibility of a family of highly disulphide bridged inhibitors. Structure, 7, 55–63.

to end of page
to top of page