Template, homology model

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. 

Homologous proteins of the CYP superfamily with known structure serve as the templates for homology modeling. The sequence similarities and/or identities between the template and target proteins should be as high as possible. Several search methods such as FASTA (40) or BLAST (41) are available to retrieve template homologs from the PDB (Protein Data Bank) (42). 

Sequence Identity (%) Among Isoenzymes Commonly Used as Template Structures for Homology Modeling and Major Human CYPs Calculated by Clustal W (43)... 

Therefore, the structures of CYPs along with all the existing homology models of the corresponding templates (please refer to the homology section in this chapter) provide the very basic information for examining CYPs from the docking point of view. Several heroic attempts have been made to use the struc-... 

Docking method Template X-ray Human homology model Group/year... 

Homology modelling is not an exact technique. Especially, when the extent of sequence homology (exact matches and matches between amino acid residues of similar property, e.g. hydrophobic, polar, acidic, basic) is low, then more attention will be paid to structural rather than sequence similarities and to prediction of structure for unmatched sequences. In such cases, and always when there is no crystal structure of a member of the family to provide a template, then total reliance has to be placed on the experience of the investigator or in one of the many computer programs now available. The principal methods have been reviewed by Sternberg (1986) and Blundell et al. (1987a). 

In a similar vein, homology modelling has been extensively used to derive 3D active site models for several cytochromes of the extensive P450 family, based on the high-resolution crystal structure of the bacterial P450cam (P-450-101) as template (Lewis and Moereels, 1992 Koymans et al., 1993b). These models have been used to explain substrate specificity. 

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