scholarly journals Corrigendum: Discovery of Small Molecule Ligands for MALAT1 by Tuning an RNA‐Binding Scaffold

2019 ◽  
Vol 58 (17) ◽  
pp. 5482-5482 ◽  
Author(s):  
Anita Donlic ◽  
Brittany S. Morgan ◽  
Jason L. Xu ◽  
Anqi Liu ◽  
Carlos Roble ◽  
...  
Keyword(s):  
Small Molecule ◽  
Rna Binding ◽  
Small Molecule Ligands

scholarly journals Berichtigung: Discovery of Small Molecule Ligands for MALAT1 by Tuning an RNA‐Binding Scaffold

2019 ◽  
Vol 131 (17) ◽  
pp. 5537-5537
Author(s):  
Anita Donlic ◽  
Brittany S. Morgan ◽  
Jason L. Xu ◽  
Anqi Liu ◽  
Carlos Roble ◽  
...  
Keyword(s):  
Small Molecule ◽  
Rna Binding ◽  
Small Molecule Ligands

scholarly journals Augmented base pairing networks encode RNA-small molecule binding preferences

2019 ◽  
Author(s):  
Carlos Oliver ◽  
Vincent Mallet ◽  
Roman Sarrazin Gendron ◽  
Vladimir Reinharz ◽  
William L. Hamilton ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Small Molecule ◽  
Binding Sites ◽  
Rna Binding ◽  
Graph Representation ◽  
Learning Approaches ◽  
Base Pairing ◽  
Binding Prediction ◽  
Structural Patterns ◽  
Small Molecule Ligands

AbstractMotivationThe binding of small molecules to RNAs is an important mechanism which can stabilize 3D structures or activate key molecular functions. To date, computational and experimental efforts toward small molecule binding prediction have primarily focused on protein targets. Considering that a very large portion of the genome is transcribed into non-coding RNAs but only few regions are translated into proteins, successful annotations of RNA elements targeted by small-molecule would likely uncover a vast repertoire of biological pathways and possibly lead to new therapeutic avenues.ResultsOur work is a first attempt at bringing machine learning approaches to the problem of RNA drug discovery. RNAmigos takes advantage of the unique structural properties of RNA to predict small molecule ligands for unseen binding sites. A key feature of our model is an efficient representation of binding sites as augmented base pairing networks (ABPNs) aimed at encoding important structural patterns. We subject our ligand predictions to two virtual screen settings and show that we are able to rank the known ligand on average in the 73rd percentile, showing a significant improvement over several baselines. Furthermore, we observe that graphs which are augmented with non-Watson Crick (a.k.a non-canonical) base pairs are the only representation which is able to retrieve a significant signal, suggesting that non-canonical interactions are an necessary source of binding specificity in RNAs. We also find that an auxiliary graph representation task significantly boosts performance by providing efficient structural embeddings to the low data setting of ligand prediction. RNAmigos shows that RNA binding data contains structural patterns with potential for drug discovery, and provides methodological insights which can be applied to other structure-function learning tasks.AvailabilityCode and data is freely available at http://csb.cs.mcgill.ca/[email protected]

scholarly journals Analysis of Small Molecule Ligands Targeting the HIV-1 Matrix Protein-RNA Binding Site

2012 ◽  
Vol 288 (1) ◽  
pp. 666-676 ◽  
Author(s):  
Ayna Alfadhli ◽  
Henry McNett ◽  
Jacob Eccles ◽  
Seyram Tsagli ◽  
Colleen Noviello ◽  
...  
Keyword(s):  
Binding Site ◽  
Small Molecule ◽  
Matrix Protein ◽  
Rna Binding ◽  
Small Molecule Ligands ◽  
Hiv 1

scholarly journals Discovery of Small Molecule Ligands for MALAT1 by Tuning an RNA‐Binding Scaffold

2018 ◽  
Vol 57 (40) ◽  
pp. 13242-13247 ◽  
Author(s):  
Anita Donlic ◽  
Brittany S. Morgan ◽  
Jason L. Xu ◽  
Anqi Liu ◽  
Carlos Roble ◽  
...  
Keyword(s):  
Small Molecule ◽  
Rna Binding ◽  
Small Molecule Ligands

Discovery of Small Molecule Ligands for MALAT1 by Tuning an RNA‐Binding Scaffold

2018 ◽  
Vol 130 (40) ◽  
pp. 13426-13431 ◽  
Author(s):  
Anita Donlic ◽  
Brittany S. Morgan ◽  
Jason L. Xu ◽  
Anqi Liu ◽  
Carlos Roble ◽  
...  
Keyword(s):  
Small Molecule ◽  
Rna Binding ◽  
Small Molecule Ligands

scholarly journals Allergens and their associated small molecule ligands ‐ their dual role in sensitization

Allergy ◽  
2021 ◽  
Author(s):  
Maksymilian Chruszcz ◽  
Fook Tim Chew ◽  
Karin Hoffmann‐Sommergruber ◽  
Barry K. Hurlburt ◽  
Geoffrey A. Mueller ◽  
...  
Keyword(s):  
Small Molecule ◽  
Dual Role ◽  
Small Molecule Ligands

Targeting FKBP isoforms with small-molecule ligands

2011 ◽  
Vol 11 (4) ◽  
pp. 365-371 ◽  
Author(s):  
Elizabeth A Blackburn ◽  
Malcolm D Walkinshaw
Keyword(s):  
Small Molecule ◽  
Small Molecule Ligands

scholarly journals Actions of the Small Molecule Ligands SW106 and AH-3960 on the Type-1 Parathyroid Hormone Receptor

2015 ◽  
Vol 29 (2) ◽  
pp. 307-321 ◽  
Author(s):  
Percy H. Carter ◽  
Thomas Dean ◽  
Brijesh Bhayana ◽  
Ashok Khatri ◽  
Raj Rajur ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Small Molecule ◽  
Hormone Receptor ◽  
Transmembrane Domain ◽  
Receptor Activation ◽  
Blood Calcium ◽  
Parathyroid Hormone Receptor ◽  
Peptide Analog ◽  
Amino Terminal ◽  
Small Molecule Ligands

Abstract The parathyroid hormone receptor-1 (PTHR1) plays critical roles in regulating blood calcium levels and bone metabolism and is thus of interest for small-molecule ligand development. Of the few small-molecule ligands reported for the PTHR1, most are of low affinity, and none has a well-defined mechanism of action. Here, we show that SW106 and AH-3960, compounds previously identified to act as an antagonist and agonist, respectively, on the PTHR1, each bind to PTHR1-delNT, a PTHR1 construct that lacks the large amino-terminal extracellular domain used for binding endogenous PTH peptide ligands, with the same micromolar affinity with which it binds to the intact PTHR1. SW106 antagonized PTHR1-mediated cAMP signaling induced by the peptide analog, M-PTH(1–11), as well as by the native PTH(1–9) sequence, as tethered to the extracellular end of transmembrane domain (TMD) helix-1 of the receptor. SW106, however, did not function as an inverse agonist on either PTHR1-H223R or PTHR1-T410P, which have activating mutations at the cytoplasmic ends of TMD helices 2 and 6, respectively. The overall data indicate that SW106 and AH-3960 each bind to the PTHR1 TMD region and likely to within an extracellularly exposed area that is occupied by the N-terminal residues of PTH peptides. Additionally, they suggest that the inhibitory effects of SW106 are limited to the extracellular portions of the TMD region that mediate interactions with agonist ligands but do not extend to receptor-activation determinants situated more deeply in the helical bundle. The study helps to elucidate potential mechanisms of small-molecule binding at the PTHR1.

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