Protein homology modeling

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Afzelins L, Zamora I, RidderstromM, AnderssonTB, Karlen A, Masimirembwa CM. Competitive CYP2C9 inhibitors enzyme inhibition stndies, protein homology modeling, and three dimensional qnantitative strnctnre activity relationship analysis. Mol Pharmacol 2001 59 909-19. 

Wang Q, Halpert JR. Combined three-dimensional qnantitative strnctnre-activity relationship analysis of cytochrome P450 2B6 snbstrates and protein homology modeling. Drug Metab Dispos 2002 30 86-95. 

Cavalli A, Greco G, Novellino E, Recanatini M. Linking CoMFA and protein homology models of enzyme-inhibitor interactions an application to nonsteroidal aromatase inhibitors. Bioorg Med Chem 2000 8 2771-80. 

Schwede T, Kopp J, Guex N et al, SWISS-MODEL an automated protein homology-modeling server. Nucleic Acids Res 2003 31 3381-3385. 

V. Use of Molecular Models of Proteins Homology Models and Docking... 

V. USE OF MOLECULAR MODELS OF PROTEINS HOMOLOGY MODELS AND DOCKING... 

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... 

Structure-based molecular modeling is another promising approach to improvement of the prediction of region-specificity of P450 metabolism. De Groot developed pharmacophore models and three-dimensional quantitative structure-activity relationships either alone or in combination with protein homology models to provide substrate-binding specificity information for CYP jgS. ... 

However, in many cases the proteins considered in the analysis are very similar and show only little structural variation. In these cases a superimposition of structurally conserved regions with standard protein homology modeling tools has yielded satisfactory protein superimpositions suited for the GRID/PCA or GRID/ GPGA analysis [8,9,13,17]. 

Several papers proposing multiple recognition sites for Pgp have been presented in the past. In this work, the pharmacophoric analysis of the dataset shows that the requirements to interact with Pgp are the same for all 129 compounds. Since in our database we have not included known R-site binders and anthracydines, we cannot say definitively that the pharmacophore found represents one of the binding sites that have been described in the literature. Two of the molecules present in the database, verapamil and dipyridamole, are known to bind in the H-site described by Shapiro and Ling [10]. We also cannot definitely state that the pharmacophore defines any functional site within the transporter. Further work, to try to define the location of the corresponding amino acids in a protein homology model, is in progress. 

If the target strucmre is unavailable from a database, it may be approximated with protein homology modeling, where a close match of protein... 

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