SNPs located within the open reading frame of a gene that result in an alteration in the amino acid sequence of the encoded protein [nonsynonymous SNPs (nsSNPs)] might directly or indirectly affect functionality of the protein, alone or in the interactions in a multi-protein complex, by increasing/ decreasing the activity of the metabolic pathway. Understanding the functional consequences of such changes and drawing conclusions about the molecular basis of diseases, involves integrating information from multiple heterogeneous sources including sequence, structure data and pathway relations between proteins. The data from NCBI's SNP database (dbSNP), gene and protein databases from Entrez, protein structures from the PDB and pathway information from KEGG have all been cross referenced into the StSNP web server, in an effort to provide combined integrated, reports about nsSNPs. StSNP provides 'on the fly' comparative modeling of nsSNPs with links to metabolic pathway information, along with real-time visual comparative analysis of the modeled structures using the Friend software application. The use of metabolic pathways in StSNP allows a researcher to examine possible disease-related pathways associated with a particular nsSNP(s), and link the diseases with the current available molecular structure data. The server is publicly available at http://glinka.bio. neu.edu/StSNP/.
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