Nucleic Acids Research, 2007, Vol. 35, Web Server issue W455–W459 doi:10.1093/nar/gkm400 The SLiMDisc server: short, linear motif discovery in proteins Norman E. Davey, Richard J. Edwards and Denis C. Shields* UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland Received January 29, 2007; Revised April 30, 2007; Accepted May 1, 2007 ABSTRACT Short, linear motifs (SLiMs) play a critical role in many biological processes, particularly in protein–protein interactions. Overrepresentation of convergent occurrences of motifs in proteins with a common attribute (such as similar subcellular loca- tion or a shared interaction partner) provides a feasible means to discover novel occurrences computationally. The SLiMDisc (Short, Linear Motif Discovery) web server corrects for common ances- try in describing shared motifs, concentrating on the convergently evolved motifs. The server returns a listing of the most interesting motifs found within unmasked regions, ranked according to an informa- tion content-based scoring scheme. It allows inter- active input masking, according to various criteria. Scoring allows for evolutionary relationships in the data sets through treatment of BLAST local align- ments. Alongside this ranked list, visualizations of the results improve understanding of the context of suggested motifs, helping to identify true motifs of interest. These visualizations include alignments of motif occurrences, alignments of motifs and their homologues and a visual schematic of the top-ranked motifs. Additional options for filtering and/or re-ranking motifs further permit the user to focus on motifs with desired attributes. Returned motifs can also be compared with known SLiMs from the literature. SLiMDisc is available at: http://bioware.ucd.ie/»slimdisc/. INTRODUCTION Short, linear motifs (SLiMs) play an essential role in the basic functions of many proteins and identifying these motifs is of great interest in expanding our understanding of biological interaction networks (1). They facilitate many fundamental biological tasks, such as subcellular targeting (e.g. The DxxLL Endosome-Lysosome- Basolateral sorting signal motif), post-translational mod- iﬁcation (e.g. The NxC N-Linked glycosylation site motif) and protein binding [e.g. The (KR)xTQT Dynein Light Chain binding motif](2). However, our current knowledge of the area is sparse with less than a hundred classes of SLiMs known in eukaryotes. Estimates have been made that suggest hundreds more are still undiscovered, making the area of SLiM discovery worthy of substantial investment of eﬀort (3). A powerful way to discover novel SLiMs comes from the fact that they are evolutionarily plastic, making them amenable to convergent evolution. SLiMs of this type can be found by searching for motifs which are shared between proteins with a common attribute (such as biological function, subcellular location or a common interaction partner) and have no evidence of a shared ancestry. This approach has been implemented for motif discovery in the LMD/DILIMOT (4,5) and Short, Linear Motif Discovery (SLiMDisc) methods (6), which incorpo- rate both masking and evolutionary ﬁltering to return overrepresented motifs. The principal underlying diﬀer- ence between the two methods is that DILIMOT masks all but one arbitrarily selected homologous protein prior to motif discovery, whereas SLiMDisc searches for motifs in all proteins and then weights results according to the evolutionarily relationships of the proteins contain- ing the motif. This article describes a web-based application of the SLiMDisc method, adding interactive masking of pro- tein features, useful data visualizations and additional ranking and ﬁltering options compared with the standa- lone program (6). While interpretation of motifs requ- ires ﬁrst a ranked scoring of the most signiﬁcant motifs, the context of the motif is of great importance in evaluating how likely it is to be of interest to investigate further. SLiMDisc permits rapid visualization of aspects of motif context, such as possible weak, uncor- rected evolutionary relationships between proteins sharing the motif, the level of disorder of the protein *To whom correspondence should be addressed. Tel: +353-1-7165344; Fax: +353-1-7166701; Email: denis.shields@ucd.ie The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors 2007 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.