Three-dimensional model, homologous proteins

Three-dimensional models can be obtained most easily if the 3D structure of a homologous protein is known (homology modelling, comparative modelling). A homology model can only be as good as the sequence... 

Homology modeling of proteins has been of great value in interpreting the relationships of sequence, structure, and function. In particular, orthologous proteins usually show a pattern of conserved residues that can be interpreted in terms of three-dimensional models of the proteins. Conserved... 

At present, starting from a protein one-dimensional sequence in order to build a three-dimensional structure is hopeless even for very short sequences. The best way to obtain access to a three-dimensional model is to perform sequence homology building, starting from an X-ray or NMR structure of a similar protein. 

PREDICTING THE THREE-DIMENSIONAL STRUCTURE OF PROTEINS BY HOMOLOGY-BASED MODEL BUILDING... 

As an example of genome-scale comparative modeling using standard sequence alignment algorithms and MODELLER, Sanchez and Sali [27] recently scanned a portion of the yeast genome, S. cerevisiae [28]. They found homologous proteins of known structure for about 17% of the proteins (1071 sequences), and they built three-dimensional models for these yeast proteins. Only 40 of these modeled proteins had a previously determined experimental structure, and 236 proteins were related to a protein of known structure for the first time. 

MJ Sutcliffe, I Haneef, D Carney, TL Blundell. Knowledge based modelling of homologous proteins. Part I Three dimensional frameworks derived from the simultaneous superposition of multiple structures. Protein Eng 1 377-384, 1987. 

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. 

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