VnD: a structure-centric database of disease-related SNPs and drugs

Abstract

Numerous genetic variations have been found to be related to human diseases. Significant portion of those affect the drug response as well by changing the protein structure and function. Therefore, it is crucial to understand the trilateral relationship among genomic variations, diseases and drugs. We present the variations and drugs (VnD), a consolidated database containing information on diseases, related genes and genetic variations, protein structures and drug information. VnD was built in three steps. First, we integrated various resources systematically to deduce catalogs of disease-related genes, single nucleotide polymorphisms (SNPs), protein mutations and relevant drugs. VnD contains 137,195 disease-related gene records (13,940 distinct genes) and 16,586 genetic variation records (1790 distinct variations). Next, we carried out structure modeling and docking simulation for wild-type and mutant proteins to examine the structural and functional consequences of non-synonymous SNPs in the drug-related genes. Conformational changes in 590 wild-type and 4437 mutant proteins from drug-related genes were included in our database. Finally, we investigated the structural and biochemical properties relevant to drug binding such as the distribution of SNPs in proximal protein pockets, thermo-chemical stability, interactions with drugs and physico-chemical properties. The VnD database, available at http://vnd.kobic.re.kr:8080/VnD/ or vandd.org, would be a useful platform for researchers studying the underlying mechanism for association among genetic variations, diseases and drugs.

Figure 1.

The workflow of the VnD database.

Figure 2.

Query table results and graphic viewer. (a) The server displays information on structures of wild-type and mutant proteins and drug docking found as results for a protein query. The ‘distance between pocket and SNP’ column indicates a pocket located close to a SNP and the distance between a pocket and SNP. The ‘structure view’ column provides the structures of the wild-type and SNP mutant proteins and docking with ligands. (b) Clicking on the gene symbol in the results table (a) allows the user to see the SNP distribution located in the gene structure, protein and disease information.