Phasing in Crystallography: A Modern Perspective

ISBN : 9780199686995

Carmelo Giacovazzo
432 ページ
197 x 247 mm
International Union of Crystallography Texts on Crystallography

Modern crystallographic methods originate from the synergy of two main research streams, the small-molecule and the macro-molecular streams. The first stream was able to definitively solve the phase problem for molecules up to 200 atoms in the asymmetric unit. The achievements obtained by the macromolecular stream are also impressive. A huge number of protein structures have been deposited in the Protein Data Bank. The solution of them is no longer reserved to an elite group of scientists, but may be attained in a large number of laboratories around the world, even by young scientists. New probabilistic approaches have been tailored to deal with larger structures, errors in the experimental data, and modest data resolution. Traditional phasing techniques like ab initio, molecular replacement, isomorphous replacement, and anomalous dispersion techniques have been revisited. The new approaches have been implemented in robust phasing programs, which have been organized in automatic pipelines usable even by non-experts. Protein structures, which 50 years ago could take months or even years to solve, can now be solved in a matter of hours, partly also due to technological advances in computer science. This book describes all modern crystallographic phasing methods, and introduces a new rational classification of them. A didactic approach is used, with the techniques described simply and logically in the main text, and further mathematical details confined to the Appendices for motivated readers. Numerous figures and applicative details illustrate the text.


1. Fundamentals of crystallography
2. Wilson statistics
3. The origin problem, invariants and seminvariants
4. The method of joint probability distribution functions, neighborhoods and representations
5. The probabilistic estimation of triplet and quartet invariants
6. Traditional direct phasing procedures
7. Joint probability distribution functions when a model is available: the Fourier syntheses
8. Phase improvement and extension
9. Charge flipping and VLD (Vive la difference)
10. Patterson methods and direct space properties
11. Phasing via electron and neutron diffraction data
12. Phasing methods for powder data
13. Molecular replacement
14. Isomorphous replacement techniques
15. Anomalous dispersion techniques
Mathematical Appendices


Carmelo Giacovazzo, Professor of Crystallography, Bari University. Director of CNR - IC Institute from 1992 to 2008. President of the European Crystallographic Association from 1997 to 2000. Winner of the European Prize Italgas 1996 for Scientific Research and Innovation; European Crystallographic Association Prize 2003. Editor of the international reviews: Zeitschrift fur Kristallographie and Croatica Chemica Acta. Scientific research: about 300 scientific papers on phasing methods, oriented both to small and to macromolecules. Some of his contributions were quoted in the Nobel Lecture by Herbert Hauptman (1985) as relevant for the solution of the phase problem for small molecules. His theoretical developments allowed to extend to about 2A the limit of the ab initio crystal structure solution of proteins, and allowed a powerful combination of traditional molecular replacement, isomorphous replacement and anomalous dispersion techniques with suitably designed probabilistic approaches.