Dysregulation of Hepatitis B Virus Nucleocapsid Assembly in vitro by RNA-binding Small Ligands

Patel, Nikesh; Abulwerdi, Fardokht A.; Fatehi, Farzad; Manfield, Iain; Grice, Stuart Le; Schneekloth, John S.; Twarock, Reidun; Stockley, Peter G.

doi:10.1016/j.jmb.2022.167557

“…gRNA was transcribed from HindIII -linearised plasmid using a T7 polymerase HiScribe kit (New England Biolabs), supplementing the reaction with 5´ amino-GMP (Jena Bioscience), according to the manufacturer's protocol. The PS1 RNA oligonucleotide [2] was purchased from IDT with a 5´ amino group. Amino-labelled RNA substrates were prepared using Alexa Fluor 488 SDP ester (Thermo Fisher) in the presence of 100 mM sodium borate buffer, at room temperature for 4 h. Labelled PS1 was gel purified, and its’ integrity confirmed using a 1% w/v formaldehyde agarose gel [2] .…”

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

“…The PS1 RNA oligonucleotide [2] was purchased from IDT with a 5´ amino group. Amino-labelled RNA substrates were prepared using Alexa Fluor 488 SDP ester (Thermo Fisher) in the presence of 100 mM sodium borate buffer, at room temperature for 4 h. Labelled PS1 was gel purified, and its’ integrity confirmed using a 1% w/v formaldehyde agarose gel [2] .…”

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Dataset of high-throughput ligand screening against the RNA Packaging Signals regulating Hepatitis B Virus nucleocapsid formation

Abulwerdi

¹

,

Fatehi

²

,

Manfield

³

et al. 2022

Data in Brief

Self Cite

0

View full text Add to dashboard Cite

Machine Learning Informs RNA‐Binding Chemical Space**

Yazdani¹,

Jordan²,

Yang³

et al. 2023

View full text Add to dashboard Cite

Small molecule targeting of RNA has emerged as a new frontier in medicinal chemistry, but compared to the protein targeting literature our understanding of chemical matter that binds to RNA is limited. In this study, we reported Repository Of BInders to Nucleic acids (ROBIN), a new library of nucleic acid binders identified by small molecule microarray (SMM) screening. The complete results of 36 individual nucleic acid SMM screens against a library of 24 572 small molecules were reported (including a total of 1 627 072 interactions assayed). A set of 2 003 RNA‐binding small molecules was identified, representing the largest fully public, experimentally derived library of its kind to date. Machine learning was used to develop highly predictive and interpretable models to characterize RNA‐binding molecules. This work demonstrates that machine learning algorithms applied to experimentally derived sets of RNA binders are a powerful method to inform RNA‐targeted chemical space.

show abstract

Machine Learning Informs RNA‐Binding Chemical Space**

Yazdani

¹

,

Jordan

²

,

Yang

³

et al. 2023

View full text Add to dashboard Cite

Small molecule targeting of RNA has emerged as a new frontier in medicinal chemistry, but compared to the protein targeting literature our understanding of chemical matter that binds to RNA is limited. In this study, we reported Repository Of BInders to Nucleic acids (ROBIN), a new library of nucleic acid binders identified by small molecule microarray (SMM) screening. The complete results of 36 individual nucleic acid SMM screens against a library of 24 572 small molecules were reported (including a total of 1 627 072 interactions assayed). A set of 2 003 RNA‐binding small molecules was identified, representing the largest fully public, experimentally derived library of its kind to date. Machine learning was used to develop highly predictive and interpretable models to characterize RNA‐binding molecules. This work demonstrates that machine learning algorithms applied to experimentally derived sets of RNA binders are a powerful method to inform RNA‐targeted chemical space.

show abstract

Dysregulation of Hepatitis B Virus Nucleocapsid Assembly in vitro by RNA-binding Small Ligands

Cited by 8 publications

References 66 publications

Dataset of high-throughput ligand screening against the RNA Packaging Signals regulating Hepatitis B Virus nucleocapsid formation

Dataset of high-throughput ligand screening against the RNA Packaging Signals regulating Hepatitis B Virus nucleocapsid formation

Machine Learning Informs RNA‐Binding Chemical Space**

Machine Learning Informs RNA‐Binding Chemical Space**

Contact Info

Product

Resources

About