Do you want BuboFlash to help you learning these things? Or do you want to add or correct something? Click here to log in or create user.



#bioinfo #publication #research #self

Given a drug D and its primary target T (in this case, FAAH), all BAs in the Protein Data Bank (PDB;12 both monomer and oligomer), are compared with the ligand-binding site of T using software SMAP.13,​14,​15 If a BA has statistically significantly similar binding site to that of T, it may be the putative off-target of D. In addition, the electrostatic potentials of the binding sites of primary target and off-target are compared to further verify the putative binding promiscuity.

Known inhibitors of T and their decoys are extracted from ChEMBL,16 and docked into T, and its putative off-targets, respectively, using protein–ligand docking software Autodock Vina.17 The distributions of docking scores of inhibitors and decoys are analyzed to verify the prediction from step 1. Then, molecular dynamics simulation is performed to characterize the conformational dynamics of the putative off-target–ligand interactions.

The concepts of genes/proteins and diseases in from PubMed abstracts (up to July 2014) are mapped to a vector space using a deep learning technique, Word2Vec.18 Semantic relations between the putative off-target and diseases are determined using the cosine similarity between vectors.

If you want to change selection, open document below and click on "Move attachment"

Molecular mechanisms involved in the side effects of fatty acid amide hydrolase inhibitors: a structural phenomics approach to proteome-wide cellular off-target deconvolution and disease association : npj Systems Biology and Applications
el, which combines tools derived from bioinformatics, systems biology, protein–ligand docking, MD (molecular dynamics) simulation and text mining, and integrates data from structural genomics, chemical genomics and literature. Full size image <span>Given a drug D and its primary target T (in this case, FAAH), all BAs in the Protein Data Bank (PDB; 12 both monomer and oligomer), are compared with the ligand-binding site of T using software SMAP. 13,​14,​15 If a BA has statistically significantly similar binding site to that of T, it may be the putative off-target of D. In addition, the electrostatic potentials of the binding sites of primary target and off-target are compared to further verify the putative binding promiscuity. Known inhibitors of T and their decoys are extracted from ChEMBL, 16 and docked into T, and its putative off-targets, respectively, using protein–ligand docking software Autodock Vina. 17 The distributions of docking scores of inhibitors and decoys are analyzed to verify the prediction from step 1. Then, molecular dynamics simulation is performed to characterize the conformational dynamics of the putative off-target–ligand interactions. The concepts of genes/proteins and diseases in from PubMed abstracts (up to July 2014) are mapped to a vector space using a deep learning technique, Word2Vec. 18 Semantic relations between the putative off-target and diseases are determined using the cosine similarity between vectors. Structural proteome-wide ligand-binding site similarity of protein BAs An increasing body of evidence supports the concept that protein fold and binding site spaces are continuous. 14,1


Summary

statusnot read reprioritisations
last reprioritisation on suggested re-reading day
started reading on finished reading on

Details


Discussion

Do you want to join discussion? Click here to log in or create user.