Protein homology reveals new targets for bioactive small molecules

Gfeller, David; Zoete, Vincent

doi:10.1093/bioinformatics/btv214

Cited by 14 publications

(14 citation statements)

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“…Moreover, targets tagged ‘(by homology)’ are predictions based on similar molecules active on proteins showing sufficient level of homology. The method was extensively detailed in a dedicated publication (13). A typical case is related to orthology, where a target is predicted for the chosen species, yet based on the similarity of the query molecule with compounds active on the ortholog proteins.…”

Section: Updatesmentioning

confidence: 99%

“…In reverse screening, the Combined-Score allows to calculate for any query molecule, assumed as bioactive, the probability to target a given protein. As 2D and 3D description of molecules are complementary, this dual scoring ligand-based reverse screening showed high performance in predicting macromolecular targets in various test sets (8) (12,13).…”

Section: Introductionmentioning

confidence: 99%

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SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules

Daina

Michielin

Zoete

2019

Nucleic Acids Research

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2,342

1,333

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SwissTargetPrediction is a web tool, on-line since 2014, that aims to predict the most probable protein targets of small molecules. Predictions are based on the similarity principle, through reverse screening. Here, we describe the 2019 version, which represents a major update in terms of underlying data, backend and web interface. The bioactivity data were updated, the model retrained and similarity thresholds redefined. In the new version, the predictions are performed by searching for similar molecules, in 2D and 3D, within a larger collection of 376 342 compounds known to be experimentally active on an extended set of 3068 macromolecular targets. An efficient backend implementation allows to speed up the process that returns results for a druglike molecule on human proteins in 15–20 s. The refreshed web interface enhances user experience with new features for easy input and improved analysis. Interoperability capacity enables straightforward submission of any input or output molecule to other on-line computer-aided drug design tools, developed by the SIB Swiss Institute of Bioinformatics. High levels of predictive performance were maintained despite more extended biological and chemical spaces to be explored, e.g. achieving at least one correct human target in the top 15 predictions for >70% of external compounds. The new SwissTargetPrediction is available free of charge (www.swisstargetprediction.ch).

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Section: Updatesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules

Daina

Michielin

Zoete

2019

Nucleic Acids Research

Self Cite

2,342

1,333

View full text Add to dashboard Cite

show abstract

“…SwissTargetPrediction is a reverse LBVS method for target fishing relying both on 2D and 3D similarity measures [26] through a dual-scoring logistic regression. The prediction is provided through a user-friendly web interface for proteins of different species [40] to allow users to easily map predictions between source organisms based on target homology. In the latest version [27], SwissTargetPrediction generates predictions by reverse screening a collection of 376,342 compounds known to be experimentally active on a set of 3068 macromolecular targets.…”

Section: Available Resources From the Swissdrugdesign Projectmentioning

confidence: 99%

Application of the SwissDrugDesign Online Resources in Virtual Screening

Daina

Zoete

2019

IJMS

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SwissDrugDesign is an important initiative led by the Molecular Modeling Group of the SIB Swiss Institute of Bioinformatics. This project provides a collection of freely available online tools for computer-aided drug design. Some of these web-based methods, i.e., SwissSimilarity and SwissTargetPrediction, were especially developed to perform virtual screening, while others such as SwissADME, SwissDock, SwissParam and SwissBioisostere can find applications in related activities. The present review aims at providing a short description of these methods together with examples of their application in virtual screening, where SwissDrugDesign tools successfully supported the discovery of bioactive small molecules.

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“…In silico molecular screening is a typical example, which requires each small molecule to be checked on beforehand for chemical structure inconsistencies, cleaned from counter-ions and other accompanying compounds, checked for the most probable tautomer, neutralized or protonated at a given pH value and potentially transformed into a 3D conformation. This automated curation process was applied meticulously during the development of the reverse screening tool SwissTargetPrediction ( www.swisstargetprediction.ch ) ( 66 – 68 ) and for the future ligand-based screening tool SwissSimilarity ( www.swisssimilarity.ch ).…”

Section: The Value Of Biocurationmentioning

confidence: 99%

The SIB Swiss Institute of Bioinformatics’ resources: focus on curated databases

Bultet¹,

Aguilar‐Rodríguez²,

Ahrens³

et al. 2015

Nucleic Acids Res

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The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article.

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Protein homology reveals new targets for bioactive small molecules

Abstract: Supplementary data are available at Bioinformatics online.

Cited by 14 publications

References 50 publications

SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules

SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules

Application of the SwissDrugDesign Online Resources in Virtual Screening

The SIB Swiss Institute of Bioinformatics’ resources: focus on curated databases

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