Protein crystallography model building

Jones T A and S Thirup 1986. Using Known Substructures in Protein Model Building and Crystallography. EMBO journal 5 819-822. 

TH Jones, S Thinip. Using known substructures in protein model building and crystallography. EMBO J 5 819-822, 1986. 

In the protein structure database PDB ( http //www. rcsb.org/pdb), by X-ray crystallography and NMR spectroscopy, experimentally solved 3D-protein structures are available to the public. Homology model building for a query sequence uses protein portions of known 3D-stmctures as structural templates for proteins with high sequence similarity. 

For many proteins, it is possible to generate structures of protein-ligand complexes quite rapidly. It is therefore not uncommon for many hundreds of structures to be determined in support of a drug discovery and optimization project. The major challenge for this level of throughput is informatics support. It is also this type of crystallography that is most in need of semiautomated procedures for structure solution and model building (see Section 12.6). 

Badger, J. (2003). An evaluation of automated model building procedures for protein crystallography. Acta Crystulhgr. D 59, 823-827. 

We will now describe some details of the interpretation of the electron-density map that has been calculated. There are two major methods used in protein crystallography to build a model of the molecule from the various features found in an electron-density map. These methods differ from those used for small-molecules because the number of atoms is so large, and because individual atoms are not resolved in most protein crystal structures. A scheme, which is a continuation of Figure 8.10 (Chapter 8), is given in Figure 9.13. 

For peptides and nucleic acids, the system should provide rapid generation of a model from sequence data in any of the commonly observed conformations (e.g., a-helix, /J-sheet, /2-turn, B-DNA, Z-DNA). For peptides, it should be possible to make insertions or deletions in the sequence easily and to mutate side chains for homology model-building applications, where the sequence of the unknown structure is mapped onto the three-dimensional structure of a sequentially homologous protein whose structure has previously been determined by X-ray crystallography. 

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