MOTIPS: Automated Motif Analysis for Predicting Targets of Modular Protein Domains

Overview

Journal BMC Bioinformatics

Publisher Biomed Central

Specialty Biology

Date 2010 May 13

PMID 20459839

Citations 18

Authors

Hugo Y K Lam

Philip M Kim

Janine Mok

Raffi Tonikian

Sachdev S Sidhu

Benjamin E Turk

Michael Snyder

Mark B Gerstein

Affiliations

Soon will be listed here.

Abstract

Background: Many protein interactions, especially those involved in signaling, involve short linear motifs consisting of 5-10 amino acid residues that interact with modular protein domains such as the SH3 binding domains and the kinase catalytic domains. One straightforward way of identifying these interactions is by scanning for matches to the motif against all the sequences in a target proteome. However, predicting domain targets by motif sequence alone without considering other genomic and structural information has been shown to be lacking in accuracy.

Results: We developed an efficient search algorithm to scan the target proteome for potential domain targets and to increase the accuracy of each hit by integrating a variety of pre-computed features, such as conservation, surface propensity, and disorder. The integration is performed using naïve Bayes and a training set of validated experiments.

Conclusions: By integrating a variety of biologically relevant features to predict domain targets, we demonstrated a notably improved prediction of modular protein domain targets. Combined with emerging high-resolution data of domain specificities, we believe that our approach can assist in the reconstruction of many signaling pathways.

Citing Articles

The carboxy-terminus, a key regulator of protein function.

Sharma S, Schiller M Crit Rev Biochem Mol Biol. 2019; 54(2):85-102.

PMID: 31106589 PMC: 6568268. DOI: 10.1080/10409238.2019.1586828.

PSSMSearch: a server for modeling, visualization, proteome-wide discovery and annotation of protein motif specificity determinants.

Krystkowiak I, Manguy J, Davey N Nucleic Acids Res. 2018; 46(W1):W235-W241.

PMID: 29873773 PMC: 6030969. DOI: 10.1093/nar/gky426.

Exhaustive search of linear information encoding protein-peptide recognition.

Kelil A, Dubreuil B, Levy E, Michnick S PLoS Comput Biol. 2017; 13(4):e1005499.

PMID: 28426660 PMC: 5417721. DOI: 10.1371/journal.pcbi.1005499.

Prediction of GCRV virus-host protein interactome based on structural motif-domain interactions.

Zhang A, He L, Wang Y BMC Bioinformatics. 2017; 18(1):145.

PMID: 28253857 PMC: 5335770. DOI: 10.1186/s12859-017-1500-8.

The Functional Human C-Terminome.

Sharma S, Toledo O, Hedden M, Lyon K, Brooks S, David R PLoS One. 2016; 11(4):e0152731.

PMID: 27050421 PMC: 4822787. DOI: 10.1371/journal.pone.0152731.

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