Computed homology

Homology modeling is discnssed in recent computational drug design texts and... 

K Sjdlander, K Karplus, M Brown, R Hughey, A Krogh, IS Mian, D Haussler. Dirichlet mixtures A method for improved detection of weak but significant protein sequence homology. Comput Appl Biosci 12 327-345, 1996. 

The World Wide Web has transformed the way in which we obtain and analyze published information on proteins. What only a few years ago would take days or weeks and require the use of expensive computer workstations can now be achieved in a few minutes or hours using personal computers, both PCs and Macintosh, connected to the internet. The Web contains hundreds of sites of Interest to molecular biologists, many of which are listed in Pedro s BioMolecular Research Tools (http // www.fmi.ch/biology/research tools.html). Many sites provide free access to databases that make it very easy to obtain information on structurally related proteins, the amino acid sequences of homologous proteins, relevant literature references, medical information and metabolic pathways. This development has opened up new opportunities for even non-specialists to view and manipulate a structure of interest or to carry out amino-acid sequence comparisons, and one can now rapidly obtain an overview of a particular area of molecular biology. We shall here describe some Web sites that are of interest from a structural point of view. Updated links to these sites can be found in the Introduction to Protein Structure Web site (http // WWW.ProteinStructure.com/). 

From the human genome project it is known, that roughly 30,000 proteins exist in humans. Currently only the 3D-structures of few thousand human pr oteins or protein domains are known. Structures of membrane-bound proteins are several magnitudes rarer. Beside efforts to solve further structures like structural genomics, there is a challenge for computational approaches to predict structures and function for homologous proteins. 

Koymans LMH, Vermeulen NPE, Baarslag A, Donne-Op den Kelder GM. A preliminary 3D model for cytochrome P450 2D6 constructed by homology model building. J Comput-Aided Mol Des 1993 7 281-9. 

However, this is not so easy without the tertiary structure of the enzyme. The possible clues are the homology search with functionally resembling enzymes and computer simulation of the tert-structure of the enzyme. The characteristic features of AMDase are (i) the reaction proceeds via an enolate-type transition state, (ii) the cysteine residue plays an essential role and (iii) the reaction involves an inversion of configuration on the a-carbon of the carboxyl group. 

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