| CPASS - Comparison of Protein Active-Site Structures |
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The Function of a Protein can be Identified by the Sequence and Structure of its Ligand-Defined Active Site The Comparison of Protein Active Site Structures (CPASS) database and software is used as part of our FAST-NMR assay to assign the function of a hypothetical protein or a protein of unknown function. The CPASS database and software enable the comparison of experimentally identified ligand-binding sites to infer biological function and aid in drug discovery. The CPASS database is comprised of ligand-defined active sites identified in the Protein Data Bank where the CPASS program compares these ligand-defined active sites to determine sequence and structural similarity without maintaining sequence connectivity. CPASS will compare any set of ligand-defined protein active sites irrespective of the identity of the bound ligand. A ligand defined active corresponds to every amino-acid in the protein that contains at least one atom within 6Å of the ligand. The CPASS database contains ~21,000 ligand-defined binding sites. The CPASS program determines the alignment of active site a with active site b from the CPASS database by maximizing an RMSD weighted BLOSUM62 scoring function (SAB):  The similarity score (S) is simply the ratio of the scoring function determined by comparing a protein target active site against a reference active site (Sab) from the CPASS database with the scoring function of a protein target active site compared against itself (Saa). S = Sab/Saa * 100 Comparison of the pyridoxal-5’phosphate defined active sites for (left) yeast hypothetical protein YBL036C (PDB ID:1B54) and (right) alanine racemase (PDB ID:1RCQ). The residues aligned by CPASS are colored blue in the structures and the active site alignments are shown below the structures. Pyridoxal-5'-phosphate is colored yellow. CPASS is run from a simple web-based entry form (password protected) and requires ~18-24 hours to complete an analysis using our 16-node Beowulf cluster. An e-mail is sent when the calculation is complete providing a link to an interactive table listing the best matches. Clicking on an entry provides a link to an interactive overlay of the ligand-defined binding sites, the identity of the protein and ligand, and the sequence alignment.
R. Powers, J. Copeland, K.
Germer, K. A. Mercier, V. Ramanathan and P. Revesz (2006) “Comparison of Protein Active-Site Structures for
Functional Annotation of Proteins and Drug Design.”
PROTEINS: Struct. Funct.
Bioinformatics,65(1):124-135.
Control results with ATP and PLP-bound Proteins Comparison of ClustalW and CPASS Examples of Functional Assignments Additional Examples of Functional Assignments |
