Human homology model

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

S Modi, MI Paine, MI Sutcliffe, L-Y Lian, WU Pnmi-ose, CR Wolfe, GCK Roberts. A model for human cytochrome P450 2d6 based on homology modeling and NMR studies of substrate binding. Biochemistry 35 4540-4550, 1996. 

Vistoli, G., Pedretti, A., Cattaneo, M., Aldini, G., Testa B. Homology modeling of human serum carnosinase, a potential medicinal target, and MD simulations of its allosteric activation by citrate. J. Med. Chem. 2006, 49, 3259-3277. 

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 ... 

Before the elucidation of the CAR X-ray crystal structure, modeling studies mainly focused on the constitutive activity of the receptor. For example, homology modeling along with molecular dynamics simulations was combined to identify critical amino acid residues responsible for the constitutive activation [43]. Especially, the role of Tyr326 as a molecular mimicry of a bound ligand in the interaction with the AF-2 helix was underscored. Mutational analyses and the later elucidation of the human CAR X-ray crystal structure confirmed an important role of this amino acid for the receptor s constitutive activity [41,44]. 

Stenham, D.R., Campbell, J.D., Sansom, M.S.P., Higgins, C.F., Kerr, I.D. and Linton, K.J. (2003) An atomic detail model for the human ATP binding cassette transporter P-glycoprotein derived from disulphide cross-linking and homology modelling. FASEB Journal, 17, 2287-2289. 

To help the reader gain a better understanding of the three-dimensional structure of the catalytic site of an esterase, Fig. 3.8 presents the 3D structure of human butyrylcholinesterase (EC 3.1.1.8) obtained by homology modeling [42], The overall structure of the enzyme is shown in Fig. 3.8, a, while Fig. 3.8,b shows a closeup of the active site with the catalytic triad highlighted and the close spatial relationship of the Ser-His-Glu residues revealed. 

Siedlecki, P., Boy, R.G., Comagic, S., Schirrmacher, R., Wiessler, M., Zielenkiewicz, P., Suhai, S. and Lyko, F. (2003) Establishment and functional validation of a structural homology model for human DNA methyltransferase 1. Biochemical and Biophysical Research Communications, 306, 558-563. 

Wang, D.-F., Helquist, P., Wiech, N.L. and Wiest, O. (2005) Toward selective histone deacetylase inhihitor design homology modeling, docking studies, and molecular dynamics simulations of human class I histone deacetylases. Journal of Medicinal Chemistry, 48, 6936-6947. 

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