MutLBSgeneDB: mutated ligand binding site gene DataBase. Issue Volume 45:Issue D1(2017) (7th October 2016)

• Record Type: Journal Article
• Authors: Kim, Pora; Zhao, Junfei; Lu, Pinyi; Zhao, Zhongming
• Is Part Of: Nucleic acids research. Volume 45:Issue D1(2017)
• Page Start: D256
• Page End: D263
• Publication Date: 2016-10-07
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkw905
• Languages: English
• ISSNs: 0305-1048

Abstract

Abstract: Mutations at the ligand binding sites (LBSs) can influence protein structure stability, binding affinity with small molecules, and drug resistance in cancer patients. Our recent analysis revealed that ligand binding residues had a significantly higher mutation rate than other parts of the protein. Here, we built mutLBSgeneDB (mutated Ligand Binding Site gene DataBase) available at http://zhaobioinfo.org/mutLBSgeneDB . We collected and curated over 2300 genes (mutLBSgenes) having ∼12 000 somatic mutations at ∼10 000 LBSs across 16 cancer types and selected 744 drug targetable genes (targetable_mutLBSgenes) by incorporating kinases, transcription factors, pharmacological genes, and cancer driver genes. We analyzed LBS mutation information, differential gene expression network, drug response correlation with gene expression, and protein stability changes for all mutLBSgenes using integrated genetic, genomic, transcriptomic, proteomic, network and functional information. We calculated and compared the binding affinities of 20 carefully selected genes with their drugs in wild type and mutant forms. mutLBSgeneDB provides a user-friendly web interface for searching and browsing through seven categories of annotations: Gene summary, Mutated information, Protein structure related information, Differential gene expression and gene-gene network, Phenotype information, Pharmacological information, and Conservation information. mutLBSgeneDB provides a useful resource for functional genomics, protein structure, drug and disease research communities.