ps52002 - Harvard-MIT Division of Health Sciences and...

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Part A: Protein structure (35 pts) The protein Bcl-2 is the product of a human proto-oncogene located on chromosome 18; it is known to causes B-cell leukemia. When reciprocal translocation occurs with this gene locus and a region of chromosome 14 that has an upstream enhancer, Bcl-2 is made in great quantity and begins to inhibit apoptosis (cell death). Let’s use this protein as an exercise in protein structure classification and prediction. I. Protein structure classification and databases (10pts) Four major protein structure classification databases are listed in chapter nine of the Mount Bioinformatics text. You will find pages 402-403, and 421-423 especially helpful with these questions. a) Briefly give one reason why MMDB would yield different structural neighbors from the other classification methods, i.e. CATH, SCOP, and FSSP. (2pts) The first step in studying the structure of a protein is to search for it in a structural classification database. Start at ( ), NCBI’s MMDB database. Search for structures of Bcl-2 in the MMDB (enter Bcl-2 in the search box). b) List two structural neighbors of Bcl-2 in the MMDB classification system. (2 pts) Select the structure entry for “Human Bcl-2, Isoform 2.” Follow the PBD ID link (1GJH) to the PDB entry for Bcl-2, isoform 2. Follow the link on the right side indicating “structural neighbors” and look at the CATH classification of Bcl-2. c) What are the classifications of this protein provided by the CATH database? (3 pts) The FSSP database is based on a structural alignment of all pair-wise combinations of the proteins in the Brookhaven structural database by the structural alignment program DALI ( d istance ali gnment tool). DALI compares existing structures using the distance matrix method and provides one convenient way to compare a new structure to existing structures in the Brookhaven structural database. d) Give a brief explanation (2-4 sentences) of the methodology of the DALI algorithm (3 pts) II. Prediction of protein secondary structure (8pts) All secondary structure prediction algorithms are based on the assumption that a given stretch of sequence is more likely to form one kind of secondary structure than another. The Ramachandran plot predicts whether a given amino acid will form an alpha helix or a beta sheet. a) What characteristics does the Ramachandran plot use to predict whether an amino acid will tend to form beta sheets or alpha helices? (1 pt)
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Most widely used methods of protein secondary structure prediction use one of three major approaches (or a combination): Chou-Fasman/GOR, neural network models, and nearest- neighbor methods. Jpred ( is a secondary structure prediction tool that runs a number of secondary prediction methods (NNSSP, DSC, predator and other nearest neighbor methods) and generates a consensus of the different outputs. Run Jpred on the Bcl-2, isoform 2 protein with the following settings:
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ps52002 - Harvard-MIT Division of Health Sciences and...

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