A structure filter for the Eukaryotic Linear Motif Resource

Current methods assessing motif accessibility do not consider much of the information available, either predicting accessibility from primary sequence or regarding any motif occurring in a globular region as low confidence. We present a method considering accessibility and secondary structural context derived from experimentally solved protein structures to rectify this situation. Putatively functional motif occurrences are mapped onto a representative domain, given that a high quality reference SCOP domain structure is available for the protein itself or a close relative. Candidate motifs can then be scored for solvent-accessibility and secondary structure context. The scores are calibrated on a benchmark set of experimentally verified motif instances compared with a set of random matches. A combined score yields 3-fold enrichment for functional motifs assigned to high confidence classifications and 2.5-fold enrichment for random motifs assigned to low confidence classifications. The structure filter is implemented as a pipeline with both a graphical interface via the ELM resource http://elm.eu.org/ webcite and through a Web Service protocol.New occurrences of known linear motifs require experimental validation as the bioinformatics tools currently have limited reliability. The ELM structure filter will aid users assessing candidate motifs presenting in globular structural regions. Most importantly, it will help users to decide whether to expend their valuable time and resources on experimental testing of interesting motif candidates.In recent years it has become clear that proteins with highly modular architectures possess numerous short peptide motifs that are essential to their function [1-5]. Such peptides are termed Linear Motifs (LM) as, in contrast to the globular domains, their function is independent of tertiary structure and encoded solely by the amino acid sequence. They are found in a diverse range of proteins, such as membrane receptors, adaptors, scaf