Homologous structures homology modeling based

Of the 517 protein kinases in the human kinome [116], structures are publicly available for < 10% of the different enzymes. In the absence of experimental data, construction of homology models based on known structures has proven a reliable method for generating 3D information. How, then, are the models built and what are the limitations of the models especially as applied to the family of protein kinases ... 

For targets that lack structural information, such as GPCRs or ion channels, a pharmacophore model or multiple pharmacophore models for different series of compounds can explain SAR and guide the synthesis of new analogs. Alternatively, homology models based on bacteriorhodopsin have been used to explain the interactions of small molecules with GPCRs. 

Fig. 4. (A) 5-HTj homology model based on the AChBP crystal structure (1I9B) showing the binding loops within two of the five subunits that make up the extracellular domain of the 5-HT3 receptor. The binding site is formed from loops A-C within the principal subunit and loops D-F in the complementary subunit. (B) Locations of the amino acids that are proposed to be within 5 A of the ligand-binding site.

Structures for the following kinases have not yet been solved. Homology models based on human kinases have been developed, however. 

Thus, EcR LBD homology models based on vertebrate nuclear receptor crystal structures, although instructive for general architecture and residue replacement, are, owing to their low sequence identity, rather speculative when used for ligand docking or as tools for virtual screens [164],... 

We have previously developed a protein homology model based on the sequence of aphid myrosinase and templates from plant myrosinase and cyanogenic P-glucosidase.12 These enzymes all adopt the (p/a)8-barrel structure typical of this... 

The 3D-structure of PFE is unknown, however it was possible to perform homology modeling based on the solved 3D-structure of a haloperoxidase from Streptomyces aur-eofaciens [25]. This revealed that both mutations are not close to the binding pocket but solely at the periphery of the enzyme [24]. 

Homology model based on SPIRO-OXINDOLE and NUTLIN MDM2 structures Constrained SP Glide docking Selection of top 20000 Compounds... 

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