Mechismo: predicting the mechanistic impact of mutations and modifications on molecular interactions.

Nucleic Acids Res 2015 Jan 11;43(2):e10. Epub 2014 Nov 11.

Cell Networks, University of Heidelberg, Im Neuenheimer Feld 267, 69120 Heidelberg, Germany Bioquant, University of Heidelberg, Im Neuenheimer Feld 267, 69120 Heidelberg, Germany

Systematic interrogation of mutation or protein modification data is important to identify sites with functional consequences and to deduce global consequences from large data sets. Mechismo (mechismo.russellab.org) enables simultaneous consideration of thousands of 3D structures and biomolecular interactions to predict rapidly mechanistic consequences for mutations and modifications. As useful functional information often only comes from homologous proteins, we benchmarked the accuracy of predictions as a function of protein/structure sequence similarity, which permits the use of relatively weak sequence similarities with an appropriate confidence measure. For protein-protein, protein-nucleic acid and a subset of protein-chemical interactions, we also developed and benchmarked a measure of whether modifications are likely to enhance or diminish the interactions, which can assist the detection of modifications with specific effects. Analysis of high-throughput sequencing data shows that the approach can identify interesting differences between cancers, and application to proteomics data finds potential mechanistic insights for how post-translational modifications can alter biomolecular interactions.

Download full-text PDF

Source
http://dx.doi.org/10.1093/nar/gku1094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4333368PMC
January 2015

Publication Analysis

Top Keywords

biomolecular interactions
8
mutations modifications
8
interactions
5
modifications
5
confidence measure
4
developed benchmarked
4
appropriate confidence
4
similarities appropriate
4
weak sequence
4
sequence similarities
4
measure protein-protein
4
protein-protein protein-nucleic
4
acid subset
4
subset protein-chemical
4
protein-nucleic acid
4
permits weak
4
interactions developed
4
protein-chemical interactions
4
protein/structure sequence
4
modifications functional
4

Similar Publications