Computer modeling

Computer modeling - BCHM464, SPRING 2011 Computer Modeling...

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BCHM464, SPRING 2011 Computer Modeling 1 Model of Alkaline Phosphatase Active Site Introduction Determination of three-dimensional structures of macromolecules is an important aspect of modern biochemistry and has contributed many recent advances in chemistry and biology. Structures of large molecules are commonly solved using either X-ray crystallography or high-resolution nuclear magnetic resonance spectroscopy (NMR). Computer software can be used to display the final structure using a list of XYZ coordinates. The graphics programs are also typically used to assist in model building and refinement of the coordinates. Other applications include investigating substrate-enzyme interactions, design of enzyme inhibitors or pharmaceuticals, and probing protein-nucleic acid interactions. In this chapter, you will use a program to examine the three-dimensional structure of alkaline phosphatase. In particular, the positions of amino acid side chains and metal ions in the active site will be studied, and interactions with the mutated side chain determined. One purpose of this exercise is to examine the three dimensional structure of AP and to be able to correlate this protein‟s structure with its function. Later in this class, you will refer to this model to locate your assigned mutant amino acid and rationalize the function of the mutated enzyme in terms of structural changes in the active site. You will use the Chimera package from the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco, developed by the Ferrin Lab at UCSF 1 to view the active site of wild type bacterial alkaline phosphatase. The structure of alkaline phosphatase in the presence of inorganic phosphate was determined by X-ray crystallography at 2.0 Å resolution. 2 The coordinates include the position of the phosphate in the active site, the location of the zinc and magnesium ions, and three water molecules that are coordinated to the magnesium. Other solvent molecules are not shown. Chimera can be downloaded free of charge from http://www.rbvi.ucsf.edu/chimera/ . On the website, you will also find a user guide and valuable tutorials. We have chosen Chimera because you can access most of its functions through the pull-down menus, but if you would like to use commands, a list of these is also in the website. Chimera is a powerful tool, but is only one of many visualization programs with different strengths and advantages. A list of other available programs can be found on the RCSB Protein Data Bank website ( http://www.pdb.org ). I. Procedure Chimera is already installed on the computers in the OWL laboratory, but you will have to download one of the alkaline phosphatase pdb files from the Protein Data Bank. 1
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Computer modeling - BCHM464, SPRING 2011 Computer Modeling...

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