mCSM-membrane: predicting the effects of mutations on transmembrane proteins
Pires, Douglas EV
Rodrigues, Carlos HM
Nucleic Acids Research
Oxford University Press
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Pires, D. E., Rodrigues, C. H., & Ascher, D. mCSM-membrane: predicting the effects of mutations on transmembrane proteins. Nucleic Acids Research https://doi.org/10.17863/CAM.52397
Significant efforts have been invested into understanding and predicting the molecular consequences of mutations in protein coding regions, however nearly all approaches have been developed using globular, soluble proteins. These methods have been shown to poorly translate to studying the effects of mutations in membrane proteins. To fill this gap, here we report, mCSM-membrane, a user-friendly web server that can be used to analyse the impacts of mutations on membrane protein stability and the likelihood of them being disease associated. mCSM-membrane derives from our well-established mutation modelling approach that uses graph-based signatures to model protein geometry and physicochemical properties for supervised learning. Our stability predictor achieved correlations of up to 0.72 and 0.67 (on cross validation and blind tests, respectively), while our pathogenicity predictor achieved a Matthew’s Correlation Coefficient (MCC) of up to 0.77 and 0.73, outperforming previously described methods in both predicting changes in stability and in identifying pathogenic variants. mCSM-membrane will be an invaluable and dedicated resource for investigating the effects of single-point mutations on membrane proteins through a freely available, user friendly web server at http://biosig.unimelb.edu.au/mcsm_membrane.
D.B.A and D.E.V.P were funded by a Newton Fund RCUK-CONFAP Grant awarded by The Medical Research Council (MRC) and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) [MR/M026302/1]; the Jack Brockhoff Foundation [JBF 4186, 2016]; Wellcome Trust (200814/Z/16/Z), and an Investigator Grant from the National Health and Medical Research Council (NHMRC) of Australia [GNT1174405]. Supported in part by the Victorian Government’s OIS Program.
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This record's DOI: https://doi.org/10.17863/CAM.52397
This record's URL: https://www.repository.cam.ac.uk/handle/1810/305312
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