George M. Sheldrick

A short history of SHELX

An account is given of the development of the SHELX system of computer programs from SHELX-76 to the present day. In addition to identifying useful innovations that have come into general use through their implementation in SHELX, a critical analysis is presented of the less-successful features, missed opportunities and desirable improvements for future releases of the software. An attempt is made to understand how a program originally designed for photographic intensity data, punched cards and computers over 10000 times slower than an average modern personal computer has managed to survive for so long. SHELXL is the most widely used program for small-molecule refinement and SHELXS and SHELXD are often employed for structure solution despite the availability of objectively superior programs. SHELXL also finds a niche for the refinement of macromolecules against high-resolution or twinned data; SHELXPRO acts as an interface for macromolecular applications. SHELXC, SHELXD and SHELXE are proving useful for the experimental phasing of macromolecules, especially because they are fast and robust and so are often employed in pipelines for high-throughput phasing. This paper could serve as a general literature citation when one or more of the open-source SHELX programs (and the Bruker AXS version SHELXTL) are employed in the course of a crystal-structure determination.

Phase annealing in SHELX-90: direct methods for larger structures

A number of extensions to the multisolution approach to the crystallographic phase problem are discussed in which the negative quartet relations play an important role. A phase annealing method, related to the simulated annealing approach in other optimization problems, is proposed and it is shown that it can result in an improvement of up to an order of magnitude in the chances of solving large structures at atomic resolution. The ideas presented here are incorporated in the program system SHELX-90; the philosophical and mathematical background to the direct-methods part (SHELXS) of this system is described.

Crystal structure refinement with SHELXL

New features added to the refinement program SHELXL since 2008 are described and explained.

SHELXT – Integrated space-group and crystal-structure determination

SHELXT automates routine small-molecule structure determination starting from single-crystal reflection data, the Laue group and a reasonable guess as to which elements might be present.

SHELXL: high-resolution refinement.

Publisher Summary SHELXL-93 was originally written as a replacement for the refinement part of the small-molecule program SHELX-76. The program is designed to be easy to use and general for all space groups and uses a conventional structure-factor calculation rather than a fast Fourier transform (FFT) summation. The latter would be faster but in practice involves some small approximations and is not suitable for the treatment of anomalous dispersion or anisotropic thermal motion. The price to pay for the extra precision and generality is that SHELXL is much slower than programs written specifically for macromolecules. This is compensated for, to some extent, by the better convergence properties, reducing the amount of manual intervention required. A new version, SHELXL-97, was released in May 1997; this is the version described in the chapter. The changes are primarily designed to make the program easier to use for macromolecules. Advances in cryogenic techniques, area detectors, and the use of synchrotron radiation enable macromolecular data to be collected to higher resolution than was previously possible. In practice, this tends to complicate the refinement because it is possible to resolve finer details of the structure. It is often necessary to model alternative conformations, and in a few cases, even anisotropic refinement is justified.

Substructure solution with SHELXD

Iterative dual-space direct methods based on phase refinement in reciprocal space and peak picking in real space are able to locate relatively large numbers of anomalous scatterers efficiently from MAD or SAD data. Truncation of the data at a particular resolution, typically in the range 3.0-3.5 A, can be critical to success. The efficiency can be improved by roughly an order of magnitude by Patterson-based seeding instead of starting from random phases or sites; Patterson superposition methods also provide useful validation. The program SHELXD implementing this approach is available as part of the SHELX package.

ShelXle: a Qt graphical user interface for SHELXL

ShelXle is a user-friendly graphical user interface for SHELXL. It combines an editor with syntax highlighting for SHELXL-associated files with an interactive graphical display for visualization of a three-dimensional structure.

Experimental phasing with SHELXC/D/E: combining chain tracing with density modification

Experimental phasing with SHELXC/D/E has been enhanced by the incorporation of main-chain tracing into the iterative density modification; this also provides a simple and effective way of exploiting noncrystallographic symmetry.

Comparison of silver and molybdenum microfocus X-ray sources for single-crystal structure determination

A detailed comparison of single-crystal diffraction data collected with Ag Kα and Mo Kα microsources (IµS) indicates that the Ag Kα data are better when absorption is significant. Empirical corrections intended to correct for absorption also correct well for the effects of the highly focused IµS beams.

Macromolecular phasing with SHELXE

Abstract SHELXE was designed to provide a simple, fast and robust route from substructure sites found by the program SHELXD to an initial electron density map, if possible with an indication as to which heavy-atom enantiomorph is correct. This should be understood as a small contribution to high-throughput structural genomics. The new sphere of influence algorithm combined with a fuzzy solvent boundary enables some chemical knowledge to be incorporated into the density modification in a general and effective manner. In the special cases of high solvent content (greater than 0.6) or very high resolution data (better than 1.5 Å) high quality maps can be produced. This raises the possibility of a new paradigm for atomic resolution structure refinement: instead of alternating atom parameter refinement with weighted electron density maps calculated with the phases of the current model, which inevitably leads to some model bias, all model building should be based on the model free experimental density map!