Using the Saccharomyces Genome Database (SGD) for analysis of protein similarities and structure

doi:10.1093/nar/27.1.74

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Nucleic Acids Research Pages 74-78

Using the Saccharomyces Genome Database (SGD) for analysis of protein similarities and structure
Introduction
Examining Protein Similarities At SGD
Protein Structure At SGD
Future Directions
Citing SGD
References

Using the Saccharomyces Genome Database (SGD) for analysis of protein similarities and structure

Stephen A. Chervitz, Erich T. Hester, Catherine A. Ball, Kara Dolinski, Selina S. Dwight, Midori A. Harris, Gail Juvik, Alice Malekian, Shannon Roberts, TaiYun Roe, Charles Scafe, Mark Schroeder, Gavin Sherlock, Shuai Weng, Yan Zhu, J. Michael Cherry* and David Botstein

Department of Genetics, Stanford University, Stanford, CA 94305-5120, USA

Received October 1, 1998; Revised and Accepted October 8, 1998

ABSTRACT

The Saccharomyces Genome Database (SGD) collects and organizes information about the molecular biology and genetics of the yeast Saccharomyces cerevisiae. The latest protein structure and comparison tools available at SGD are presented here. With the completion of the yeast sequence and the Caenorhabditis elegans sequence soon to follow, comparison of proteins from complete eukaryotic proteomes will be an extremely powerful way to learn more about a particular protein's structure, its function, and its relationships with other proteins. SGD can be accessed through the World Wide Web at http://genome-www.stanford.edu/Saccharomyces/

INTRODUCTION

The Saccharomyces Genome Database (SGD) exists to provide the scientific community with access to the Saccharomyces cerevisiae sequence and the wealth of associated information. This database includes a variety of biological information, including the complete, annotated DNA and protein sequence along with several tools for sequence analysis. Many of these features have been recently described (1,2). Here we focus on features of SGD that provide users with tools for comparing yeast protein sequences and examining protein structure. Sequence comparisons play a critical role in the initial process of determining the function of specific proteins and also in interpreting new protein sequence data from large-scale genome sequencing projects. There are several sequence comparison tools at SGD. Here, we discuss the Genome-wide Protein Similarity View program, which is a powerful tool for examining protein similarities. Like the expanding base of sequence information, there is also a growing amount of structural information. Sacch3D is a feature of SGD that organizes and presents structural information about yeast proteins and their putative homologs. Familiarity with tools such as those described here will enable molecular biologists and geneticists to gain insight into the function and possible evolution of their protein of interest.

EXAMINING PROTEIN SIMILARITIES AT SGD

The Genome-wide Protein Similarity View (GPSV), at URL http://genome-www.stanford.edu/cgi-bin/SGD/SWA/swaEntryForm.pl , displays, either graphically or in a table, all the ORFs in the S.cerevisiae genome that are similar to a given query ORF based on a Smith-Waterman protein sequence comparison (3). Smith-Waterman comparisons were conducted on a TimeLogic DeCypher II machine using the affine Smith-Waterman application (4). This system uses the pscorer program to calculate a P-value (5). More details of the Smith-Waterman alignment are available at the GPSV help page (URL in Table 1).

Table 1. URLs mentioned in this review

The GPSV graphic view, a Java applet, represents all 16 yeast nuclear chromosomes as horizontal black bars, with centromeres and positional coordinates indicated (Fig. 1A). Superimposed on the black chromosome bars are small vertical colored bars (similarity bars) that represent ORFs predicted by the Smith-Waterman analysis to have significant protein sequence similarities. A small black rectangle surrounds the bar for the query ORF itself. Its ORF name and associated standard gene name are displayed in the upper right hand corner. The color of the bars indicates the relative similarity shared with the query ORF. The warm colors (red) indicate high similarity while the cool colors (blue) indicate lower similarity. The user can switch between different query ORFs, add ORFs to the query list, and change several parameters of the similarity display.

A
B

Figure 1. The Genome-Wide Protein Similarity View page. Features are discussed in detail in the text. (A) The Genome-Wide Protein Similarity View graphic view; (B) Genome-Wide Protein Similarity View parameters.

Immediately below the graphic display are seven fields that contain additional information about the query and target ORFs (Fig. 1B). The first field displays a constantly updated readout of the current location of the mouse cursor in terms of base pairs along the chromosomes and the names of genes or ORFs selected by the mouse. The remaining fields contain information when the cursor is positioned over a similarity bar. The classes of information are: (i) P-Value (the P-value for the similarity between the query ORF and the target ORF); (ii) % Aligned (the percent of the query sequence that is aligned with the target sequence); and (iii) Gaps (the number of gaps inserted in the query sequence to achieve the alignment).

Each similarity bar can be clicked to reach more information about the target ORF. Options include links to the SGD Locus and Gene/Sequence Resources pages for the target ORF, an alignment of the query and target amino acid sequences, the DNA Similarity View, which displays the alignment of the target and query ORF DNA sequences, and the Protein Similarity View, where the selected target ORF is used as the query ORF.

The protein similarity data can also be displayed as a table, which can be accessed from the graphic display page or from the ORF input form. The table lists target ORFs in order of decreasing similarity to the query ORF, as determined by P-value; the target ORFs can also be sorted by percent identity. For each target ORF, the table lists the same information and links as the graphic display.

PROTEIN STRUCTURE AT SGD

The Sacch3D feature at SGD (at URL http://genome-www.stanford.edu/Sacch3D/ ) provides structural information for S.cerevisiae proteins by integrating data from SGD and structural databases and presenting it via up-to-date, concise summaries and links to structural resources. Sacch3D supplies researchers both within and outside the yeast community with insight into the structure and putative function of yeast proteins. Structural information for Sacch3D is obtained primarily by BLASTP analysis (6,7) of the Brookhaven Protein Database (PDB) (8,9) to identify all PDB structures with significant sequence (and therefore likely structural) similarity to yeast proteins. Results are updated monthly to keep pace with the growth of the PDB. To reduce the redundancy in the PDB and thus simplify the BLAST analysis, all PDB protein sequences are first clustered into groups of closely related sequences (see the on-line help at the Sacch3D website for details; Table 1) before the BLAST is run. As of September 1998, 18% of yeast proteins have either a known structure or putative homolog in a clustered version of the PDB (Table 2). The Sacch3D search utility provides a structural information page for all ORFs in the yeast genome (example shown in Fig. 2). This page contains information provided by both internal and external resources. A summary table is presented showing PDB structures for the yeast protein (if a structure can be identified) and proteins with which it shares significant sequence similarity. For each structure, there are links to a variety of freely available 3D viewers (Fig. 3) and external structural databases. 3D viewers include RasMol (10), Webmol Java viewer (11), Chime (MDL Information Systems, www.mdli.com) and Cn3D (12). External structural databases include PDB (8,9), SCOP (13,14), CATH (15), PDBsum (16), ModBase (17), Macromolecular Movements Database (18) and MMDB (19). The PDB similarities are listed from best to worst (based on BLASTP P-value) and are clustered to facilitate browsing. That is, one representative structure is listed in cases where there are multiple variants of the same structure (mutants or complex forms). Access to the neighboring structures is also provided.

	N	Percent
Total yeast proteins	6215	100
Identified genetically	3086	50
With known 3D structure(s)^a	52	0.8
With PDB homolog(s)	1110	18
With PDB homolog and identified genetically	848	13

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