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VnD:一个以结构为中心的疾病相关单核苷酸多态性和药物数据库。

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

作者信息

Yang Jin Ok, Oh Sangho, Ko Gunhwan, Park Seong-Jin, Kim Woo-Yeon, Lee Byungwook, Lee Sanghyuk

机构信息

Korean BioInformation Center, Korea Research Institute of Bioscience and Biotechnology, 111 Gwahangno, Yuseong-gu, Daejeon 305-806, Korea.

出版信息

Nucleic Acids Res. 2011 Jan;39(Database issue):D939-44. doi: 10.1093/nar/gkq957. Epub 2010 Nov 4.

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.

摘要

人们发现众多基因变异与人类疾病相关。其中很大一部分还会通过改变蛋白质结构和功能来影响药物反应。因此,了解基因组变异、疾病和药物之间的三边关系至关重要。我们推出了变异与药物(VnD)数据库,这是一个整合了疾病、相关基因和基因变异、蛋白质结构及药物信息的数据库。VnD分三步建成。首先,我们系统整合了各种资源,以推导疾病相关基因、单核苷酸多态性(SNP)、蛋白质突变及相关药物的目录。VnD包含137,195条疾病相关基因记录(13,940个不同基因)和16,586条基因变异记录(1790个不同变异)。接下来,我们对野生型和突变型蛋白质进行了结构建模和对接模拟,以研究药物相关基因中非同义SNP的结构和功能后果。我们的数据库纳入了来自药物相关基因的590个野生型和4437个突变型蛋白质的构象变化。最后,我们研究了与药物结合相关的结构和生化特性,如近端蛋白质口袋中SNP的分布、热化学稳定性、与药物的相互作用以及物理化学性质。VnD数据库可通过http://vnd.kobic.re.kr:8080/VnD/ 或vandd.org访问,它将为研究基因变异、疾病和药物之间关联潜在机制的研究人员提供一个有用的平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7142/3013797/7e7a68ec0fad/gkq957f1.jpg

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