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Surface Analysis of a Protein Using CASTp





  • To get a detailed and complete quantitative characterization of surface pockets and interior voids of proteins using CASTp (Computed Atlas of Surface Topography of proteins).


  • To familiarize with the online resource CASTp.




Proteins are one of the important fundamental units of all living cells. Proteins have a wide range of functions within all the living beings. Some of the important functions such as DNA replication, catalysis of metabolic reactions, transportation of molecules from one location to another etc. are performed with the help of proteins.


The building blocks of proteins are amino acids. Amino acids are made from an amine (-NH2) and a carboxylic acid (-COOH) functional groups as well as a side chain which is specific to each amino acid. There are almost 20 amino acids found in human body that usually varies in their R groups. In proteins, the amino acids are linked to each other by means of peptide bonds. A peptide bond is formed when the carboxyl group of one amino acid is linked to the amino group of another molecule through a covalent bond.


Proteins differ from one another in their structure, primarily in their sequence of amino acids. The structure explains the different levels of organization of a protein molecule. The protein structure is classified into primary, secondary, tertiary, and quaternary. The linear sequence the polypeptide chain of amino acid refers to the primary structure of proteins. The intermolecular and intra-molecular hydrogen bonding between the amide groups in primary structure of protein form secondary structure. Alpha helices and beta sheets are the two important secondary structures in protein. The three dimensional structure of a single protein molecule refers to the tertiary structure. The quaternary structure is formed by several protein molecules or polypeptide chains.


The interaction with molecules such as substrate, ligand, DNA and other domains helps the proteins to carry out its specific function. The three-dimensional structure of protein gives the required shape and physicochemical features to facilitate such interactions. The relationship between the protein structure and its function can be studied through the structural information of protein surface regions. Particularly, a study of protein surface regions enables to understand the enzyme mechanism, which helps to determine the binding specificity. Also, the biological functions of protein structures (newly solved) with an unknown function can be identified.




The CASTp (Computed Atlas of Surface Topography of proteins) web server is an online tool that locates, measure and characterizes the pockets on the protein surfaces and the voids in the interior of proteins. These surface pockets and voids are the concave regions of proteins that are usually correlated with binding activities. CASTp uses the alpha shape and the pocket algorithm developed in computational geometry (Jie Liang et al., 2003) to delineate and measure the surface pockets and voids in proteins. In CASTp, the surface pockets are explained as concave regions of proteins with binding sites at the opening. These pockets also allow easy access of water molecules from exterior. The voids are described as hidden vacant spaces in the interior of proteins, which are inaccessible to water molecules after removing all hetero atoms from exterior.



Figure 1: The binding pocket (green) of HIV-1 protease (1hte). The ligand Gr12397(yellow) occupies the binding site.

Image source: http://sts.bioengr.uic.edu/castp/examples.php


The CASTp online tool analyzes all surface pockets and interior voids on three dimensional structure of a protein and also it gives a detailed characterization of all the atoms associated in the formation of these voids and pockets. CASTp uses both the solvent accessible surface model (Richards' surface) and molecular surface model (Connolly's surface) to analytically measure the area and volume of each void and pocket. Solvent accessible surface area otherwise known as Richards’ molecular surface is the surface area of a biomolecule that is accessible to a solvent. Besides this, CASTp also measures the size of each pockets and mouth openings. This enables to determine the accessibility of binding sites to different ligands and substrates. The computation or surface analysis of proteins using CASTp has a number of advantages in biological studies.


The annotated functional information of proteins is also included in the new version of CASTp. These annotations are derived from the Protein Data Bank (PDB), Swiss-Prot, as well as Online Mendelian Inheritance in Man (OMIM), and the latter contains information on the variant single nucleotide polymorphisms (SNPs) that are known to cause disease.




  This experiment uses the CASTp online resource, available through http://cast.engr.uic.edu

Joe Dundas, Zheng Ouyang, Jeffery Tseng, Andrew Binkowski, Yaron Turpaz, and Jie Liang. 2006. CASTp: computed atas of surface topography of proteins with structural and topographical mapping of functionally annotated residues. Nucl. Acids Res., 34:W116-W118.





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