title: mCSM-NA: predicting the effects of mutations on protein-nucleic acids interactions.
abstract: Over the past two decades, several computational methods have been proposed to predict how missense mutations can affect protein structure and function, either by altering protein stability or interactions with its partners, shedding light into potential molecular mechanisms giving rise to different phenotypes. Effectively and efficiently predicting consequences of mutations on protein-nucleic acid interactions, however, remained until recently a great and unmet challenge. Here we report an updated webserver for mCSM-NA, the only scalable method we are aware of capable of quantitatively predicting the effects of mutations in protein coding regions on nucleic acid binding affinities. We have significantly enhanced the original method by including a pharmacophore modelling and information of nucleic acid properties into our graph-based signatures, considering the reverse mutation and by using a refined, more reliable data set, based on a new release of the ProNIT database, which has significantly improved the reliability and applicability of the methodology. Our new predictive model was capable of achieving a correlation coefficient of up to 0.70 on cross-validation and 0.68 on blind-tests, outperforming its previous version. The server is freely available via a user-friendly web interface at: http://structure.bioc.cam.ac.uk/mcsm_na.
authors.affiliation: Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Brazil.
authors.forename: Douglas E V
authors.initials: DEV
authors.lastname: Pires
authors.affiliation: Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Brazil.|Department of Biochemistry, University of Cambridge, Cambridge, UK.|Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Australia.
authors.forename: David B
authors.initials: DB
authors.lastname: Ascher
mesh_terms: D001665:Binding Sites; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020407:Internet; D000069550:Machine Learning; D008958:Models, Molecular; D015233:Models, Statistical; D020125:Mutation, Missense; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D059386:Reverse Genetics; D012984:Software; D013816:Thermodynamics
chemical_list: D004268:DNA-Binding Proteins; D016601:RNA-Binding Proteins; D004247:DNA