Structure validation

Platon/System S Single crystal structure validation with the program PLATON, A. L. Spek, J. Appl. Crystallogr., 2003, 36, 7 13 

Shelxl97 SHELX97 Programs for Crystal Structure Analysis (Release 97 2). G. M. Sheldrick, Institiit fiir Anorganische Chemie der Universitat, Tammanstrasse 4, D 3400 Gottingen, Germany, 1998 

Sir2002/CAOS SIR2004 an improved tool for crystal structure determination and refinement, M. C. Burla, R. Caliandro, M. Camalli, B. Carrozzini, G. L. Cascarano, L. De Caro, C. Giacovazzo, G. Polidori and R. Spagna, J. Appl. Crystallogr., 2005, 38, 381 388 

Xhydex Indirect Location of Hydride Ligands in Metal Cluster Complexes, A. G. Orpen, J. Chem. Soc., Dalton Trans., 1980, 2509 2516 

Xtal (GPL d) Xtal3.7 System. S. R. Hall, D. J. du Boulay and R. Olthof Hazekamp, Eds., University of Western Australia. (2000) http //xtal.sourceforge.net/ 

This chapter will point out some of the more common and avoidable pitfalls. Readily available computer software will be discussed that generates appropriate ALERTS when something unusual or inconsistent is detected. The analyst should, of course, understand the meaning of a particular ALERT and be able to respond with proper action. 

A crystal stmcture determination is not finished with the refinement to convergence of the structural model parameters such as the positional and displacement parameters. Incorrect models may well result in satisfactory looking convergence of the least-squares refinement. The model has to be analyzed in detail in a process called stracture validation. In particular, the model should make chemical sense. An incorrect model may easily lead to disastrous conclusions about the underlying chemistry. Examples can be formd in Harlow (1996) and Spek (2003). 

The starting point of automated structure validation was the creation of a universal computer readable data format, named GIF (Hall et a/., 1991), for reporting the re suits 

Structure validation should give an answer to the following three questions  

The answer to this question is easily handled with a checklist of items to be reported in order to be able to repeat the study. Consistency is also easily checked. Examples are the comparison of the volume as calculated from the cell dimensions with the reported volume and the density calculated from the cell content as derived from the coordinate list and symmetry with the reported density. 

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CM Topham, N Snmvasan, CJ Thorpe, IP Ovenngton, NA Kalsheker. Comparative modelling of major house dust mite allergen der p I Structure validation using an extended environmental ammo acid propensity table. Protein Eng 7 869-894, 1994. 

The increased speed of structure determination necessary for the structural genomics projects makes an independent validation of the structures (by comparison to expected properties) particularly important. Structure validation helps to correct obvious errors (e.g. in the covalent structure) and leads to a more standardised representation of structural data, e.g. by agreeing on a common atom name nomenclature. The knowledge of the structure quality is a prerequisite for further use of the structure, e.g. in molecular modelling or drug design. 

This structure validates a point made earlier, that ligand access occurs in the indicated position. At the point where this plausible but unproven assertion was first made, the reference was to reactions in which pyridine N-oxides were acting as oxygen donors. It remains pertinent for ligand substitution as well, but also for oxygen transfer reactions where sulfoxides are the oxygen donor atoms. 

Voigt-Martin et al. [13] have used MICE to solve the stmcture of 4-(4 -(N,N-dimethyl)aminobenzylidene)-pyrazolidine-3,5-dione at 1.4A in projection using 42 reflections. The potential maps do not resolve atoms with these data and models have to be fitted to the map density in a way reminiscent of macromolecular crystallography. This can pose problems in structure validation which were overcome in this case by simulation calculations. There is an excellent agreement between the solution and independent model building and high resolution electron microscopy studies. 

Validation Once a structure has been determined, it is validated using a custom structure validation system (Badger and Hendle, 2002) to detect local errors. The system is based on PROCHECK (Morris efaJ., 1992), WHATCHECK(Vriend, 1990), SFCHECK (Vaguine ef ah, 1999), and PHISTATS and OVFRLAPMAP (from CCP4). 

MolProbity (Lovell et al., 2003) is an interactive macromolecular structure validation and visualization tool from the Richardsons laboratory (molpro-bity.biochem.duke.edu). The program may be run interactively using a Java-enabled web browser, or downloaded to your PC. The latest version was run over the web. 

Accessing software for electron density fitting and structure validation... 

K. A. Palmer and H. A. Scheraga, J. Comput. Chem., 12, 505 (1991). Standard-Geometry Chains Fitted to X-ray Derived Structures Validation of the Rigid-Geometry Approximation. I. Chain Closure Through a Limited Search of Loop Conformations. 

Barone, G. Gomez-Paloma, L. Duca, D. Silvestri, A. Riccio, R. Bifulco, G. Structure validation of natural products by quantum-mechanical GIAO calculations of C NMR chemical shifts, Chem.-Eur, J. 2002,8, 3233-3239. 

Peptoid helices are detected in structure-supporting solvents even in relatively short oligomers. Because intramolecular C=0- H-N H-bond formation cannot be the driving force for peptoid secondary structure, the steric influence of the bulky and chiral side chain is likely to provide the required constraint. Interactions between side-chain groups, and between side chains and the carbonyls of the main-chain amides, may add stability to the ordered secondary structure. However, for very short oligomers (34) or peptoids based on N-substituted a-amino acids with a small side chain (35), such as Nala (also termed sarcosine, Sar, 9), complex mixtures of conformers associated with either cis or trans tertiary amide groups have been detected. In addition to the classic CD technique, the contribution of other spectroscopies, such as pulsed ESR (36), may be of value for the 3-D structural validation of peptoid molecules. 

As another measure of structure validity, the CD spectrum of wild-type JHE was determined to compare the amount of a helical secondary structure calculated from the spectrum with that observed in the model. Deconvolution of the data in the wavelength region of 200 to 300 nm yields 36% a helix (J. Magdalou, personal communication). This compares to 30 % a helix in our JHE model. 

Summary of relevant pharmaceutical data including chemical structural formula, synthetic route of active substcmce(s), structure validation, pharmaceutical description, composition (qualitative and quantitative), ingredient eind finished product specifications (or trial batch characterisation) and analytical methods, method of manufacture and sissembly of product, stability and storage precautions, container description, eUid bioavailability. 

Various single crystal suites have programs useful for structure analysis, including finding the reduced cell, checking if the structure has already been solved, structure visualization and structure validation. Most Rietveld... 

While computer-based structure validation is integrated in single crystal software, it is somewhat lagging in the powder diffraction community. Ton Spek s... 

Platon/ Single crystal structure validation with the Platon requires Shelx... 

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