Rocco Caliandro

SIR2004: an improved tool for crystal structure determination and refinement

SIR2004 is the evolution of the SIR2002 program [Burla, Camalli, Carrozzini, Cascarano, Giacovazzo, Polidori & Spagna (2003). J. Appl. Cryst. 36, 1103]. It is devoted to the solution of crystal structures by direct and Patterson methods. Several new features implemented in SIR2004 make this program efficient: it is able to solve ab initio both small/medium-size structures as well as macromolecules (up to 2000 atoms in the asymmetric unit). In favourable circumstances, the program is also able to solve protein structures with data resolution up to 1.4–1.5 A, and to provide interpretable electron density maps. A powerful user-friendly graphical interface is provided.

IL MILIONE: a suite of computer programs for crystal structure solution of proteins

IL MILIONEIl Milione is the title of the book by Marco Polo, dictated to Rustichello da Pisa in 1298 in the Genova prison where Marco was imprisoned after a naval battle between Genova and Venezia. Il Milione is a travel report: the name suggests the millions of marvels seen during the travel. Most contemporaries thought that they were a million tales. Our program is also a travel report, but in the world of crystallography. is a suite of computer programs devoted to protein crystal structure determination by X-ray crystallography. It may be used in the following key activities. (a) Ab initio phasing, via Patterson or direct methods. The program may succeed even with structures with up to 6000 non-H atoms in the asymmetric unit, provided that atomic resolution is available, and with data at quasi-atomic resolution (1.4–1.5 A). (b) Single or multiple isomorphous replacement, single- or multiple-wavelength anomalous diffraction, and single or multiple isomorphous replacement with anomalous scattering techniques. In the first step the program finds the heavy-atom/anomalous scatterer substructure, then automatically uses the above information to phase protein reflections. Phase extension and refinement are performed by electron density modification techniques. (c) Molecular replacement. The orientation and the location of the protein molecules are found via reciprocal space methods. Phase extension and refinement are performed by electron density modification techniques. All the programs integrated into IL MILIONE are controlled by means of a user-friendly graphical user interface, which is used to input data and to monitor intermediate and final results by means of real-time updated messages, diagrams and histograms.

SIR2011: a new package for crystal structure determination and refinement

SIR2011, the successor of SIR2004, is the latest program of the SIR suite. It can solve ab initio crystal structures of small- and medium-size molecules, as well as protein structures, using X-ray or electron diffraction data. With respect to the predecessor the program has several new abilities: e.g. a new phasing method (VLD) has been implemented, it is able to exploit prior knowledge of the molecular geometry via simulated annealing techniques, it can use molecular replacement methods for solving proteins, it includes new tools like free lunch and new approaches for electron diffraction data, and it visualizes three-dimensional electron density maps. The graphical interface has been further improved and allows the straightforward use of the program even in difficult cases.

Crystal structure determination and refinement via SIR2014

SIR2014 is the latest program of the SIR suite for crystal structure solution of small, medium and large structures. A variety of phasing algorithms have been implemented, both ab initio (standard or modern direct methods, Patterson techniques, Vive la Difference) and non-ab initio (simulated annealing, molecular replacement). The program contains tools for crystal structure refinement and for the study of three-dimensional electron-density maps via suitable viewers.

Automatic structure determination from powder data with EXPO2004

EXPO2004 is the updated version of the EXPO program [Altomare et al. (1999). J. Appl. Cryst. 32, 339–340]. The traditional steps of the ab initio powder solution process are performed automatically: indexing, space-group determination, decomposition of the pattern for extracting the observed structure-factor moduli, structure solution by direct methods, model refinement by Rietveld technique. Special strategies may be applied to improve both the estimates of the extracted structure-factor moduli and the quality of the structure model. In addition, the use of special procedures exploiting available supplementary information on molecular geometry can be successfully adopted. The graphical interface has also been improved.

Kinematic diffraction on a structure with periodically varying scattering function.

A theory is developed to describe the kinematic diffraction response of a crystal when it is subjected to a periodically varying external perturbation. It is shown that if a part of the local electron density varies linearly with an external stimulus, the diffracted signal is not only a function of the stimulation frequency Ω, but also of its double 2Ω. These frequency components can provide, under certain conditions, selective access to partial diffraction contributions that are normally summed up in the interference pattern. A phasing process applied to partial diffraction terms would allow recovery of the substructure actively responding to the stimulus. Two ways of frequency filtering are discussed (demodulation and correlation) with respect to extracting information from such an experiment. Also considered is the effect of the variation of different structural parameters on the diffraction intensity that have to be accounted for while planning modulation-enhanced experiments. Finally, the advantages and limitations of the proposed concept are discussed, together with possible experiments.

Space-group determination from powder diffraction data: a probabilistic approach

Experimental powder diffraction diagrams, once indexed and decomposed into single diffraction intensities, can be submitted to statistical analysis for the determination of space-group symmetry. A new algorithm is illustrated, which is able to provide, on a quantitative basis, a probability value for each extinction symbol compatible with the previously established lattice symmetry. The algorithm has been implemented in EXPO2004 [Altomare, Caliandro, Camalli, Cuocci, Giacovazzo, Moliterni & Rizzi (2004). J. Appl. Cryst. 37, 1025–1028] and has been successfully tested using a large set of experimental data.

Ab initio phasing of proteins with heavy atoms at non-atomic resolution: pushing the size limit of solvable structures up to 7890 non-H atoms in the asymmetric unit

The success of the ab initio phasing process mainly depends on two parameters: data resolution and structural complexity. In agreement with the Sheldrick rule, the presence of heavy atoms can also play a nonnegligible role in the success of direct methods. The increased efficiency of the Patterson methods and the advent of new phasing techniques based on extrapolated reflections have changed the state of the art. In particular, it is not clear how much the resolution limit and the structural complexity may be pushed in the presence of heavy atoms. In this paper, it is shown that the limits fixed by the Sheldrick rule may be relaxed if the structure contains heavy atoms and that ab initio techniques can succeed even when the data resolution is about 2 A, a limit unthinkable a few years ago. The method is successful in solving a structure with 7890 non-H atoms in the asymmetric unit at a resolution of 1.65 A, a considerable advance on the previous record of 6319 atoms at atomic resolution.

The difference electron density: a probabilistic reformulation.

The joint probability distribution function P(E, E(p)), where E and E(p) are the normalized structure factors of the target and of a model structure, respectively, is a fundamental tool in crystallographic methods devoted to crystal structure solution. It plays a central role in any attempt for improving phase estimates from a given structure model. More recently the difference electron density rho(q) = rho - rho(p) has been revisited and methods based on its modifications have started to play an important role in combination with electron density modification approaches. In this paper new coefficients for the difference electron density have been obtained by using the joint probability distribution function P(E, E(p), E(q)) and by taking into account both errors in the model and in measurements. The first applications show the correctness of our theoretical approach and the superiority of the new difference Fourier synthesis, particularly when the model is a rough approximation of the target structure. The new and the classic difference syntheses coincide when the model represents the target structure well.

Direct methods and simulated annealing: a hybrid approach for powder diffraction data

The solution of crystal structures from powder data using direct methods can be very difficult if the quality of the diffraction pattern is low and if no heavy atoms are present in the molecule. On the contrary, the use of direct-space methods does not require good quality diffraction data, but if a molecular model is available, the structure solution is limited principally by the number of degrees of freedom used to describe the model. The combination of the information contained in the electron density map (direct methods) with the Monte Carlo method, which uses simulated annealing as a global minimization algorithm (direct-space techniques), can be a useful tool for crystal structure solution, especially for organic structures. A modified and improved version of this approach [Altomare et al. (2003), J. Appl. Cryst. 36, 230–238] has been implemented in the EXPO2004 program and is described here.