Author | Pires, Douglas Eduardo Valente | |
Author | Blundell, Tom Leon | |
Author | Ascher, David Benjamin | |
Access date | 2017-05-03T17:22:58Z | |
Available date | 2017-05-03T17:22:58Z | |
Document date | 2016 | |
Citation | PIRES, Douglas Eduardo Valente; BLUNDELL, Tom Leon; ASCHER, David B. mCSM-lig: quantifying the effects of mutations on protein-small molecule affinity in genetic disease and emergence of drug resistance. Scientific Reports 6, Art. 29575, 2016 | pt_BR |
ISSN | 2045-2322 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/18719 | |
Language | eng | pt_BR |
Publisher | Springer Nature | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | modelos computacionas | pt_BR |
Title | mCSM-lig: quantifying the effects of mutations on protein-small molecule affinity in genetic disease and emergence of drug resistance. | pt_BR |
Type | Article | pt_BR |
DOI | 10.1038/srep29575 | |
xmlui.metadata.dc.description.abstractes | The ability to predict how a mutation affects ligand binding is an essential step in understanding, anticipating and improving the design of new treatments for drug resistance, and in understanding genetic diseases. Here we present mCSM-lig, a structure-guided computational approach for quantifying the effects of single-point missense mutations on affinities of small molecules for proteins. mCSM-lig uses graph-based signatures to represent the wild-type environment of mutations, and small-molecule chemical features and changes in protein stability as evidence to train a predictive model using a representative set of protein-ligand complexes from the Platinum database. We show our method provides a very good correlation with experimental data (up to ρ = 0.67) and is effective in predicting a range of chemotherapeutic, antiviral and antibiotic resistance mutations, providing useful insights for genotypic screening and to guide drug development. mCSM-lig also provides insights into understanding Mendelian disease mutations and as a tool for guiding protein design. mCSM-lig is freely available as a web server at http://structure.bioc.cam.ac.uk/mcsm_lig.
HERZIG, Volker et al. Molecular basis of the remarkable species selectivity of an insecticidal sodium channel toxin from the African spider Augacephalus ezendami. Scientific Reports 6, Art. 29538, 2016 | pt_BR |
Affilliation | University of Cambridge. Sanger Building. Department of Biochemistry. Cambridge, CB, UK/ Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil | pt_BR |
Affilliation | University of Cambridge. Sanger Building. Department of Biochemistry. Cambridge, CB, UK | pt_BR |
Affilliation | University of Cambridge. Sanger Building. Department of Biochemistry. Cambridge, CB, UK | pt_BR |
Subject | Computational models | pt_BR |
Subject | Machine learning | pt_BR |
Subject | Protein analysis | pt_BR |