W526–W531 Nucleic Acids Research, 2009, Vol. 37, Web Server issue doi:10.1093/nar/gkp316 Published online 6 May 2009 ProSMoS server: a pattern-based search using interaction matrix representation of protein structures Shuoyong Shi1, Bhadrachalam Chitturi2 and Nick V. Grishin1,2,* 1Howard Hughes Medical Institute and 2Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9050, USA Received February 18, 2009; Revised April 7, 2009; Accepted April 16, 2009 ABSTRACT Assessing structural similarity and defining common regions through comparison of protein spatial structures is an important task in functional and evolutionary studies of proteins. There are many servers that compare structures and define sub- structures in common between proteins through superposition and closeness of either coordinates or contacts. However, a natural way to analyze a structure for experts working on structure classifi- cation is to look for specific three-dimensional (3D) motifs and patterns instead of finding common fea- tures in two proteins. Such motifs can be described by the architecture and topology of major secondary structural elements (SSEs) without consideration of subtle differences in 3D coordinates. Despite the importance of motif-based structure searches, currently there is a shortage of servers to perform this task. Widely known TOPS does not fully address this problem, as it finds only topological match but does not take into account other important spatial properties, such as interactions and chirality. Here, we implemented our approach to protein structure pattern search (ProSMoS) as a web- server. ProSMoS converts 3D structure into an inter- action matrix representation including the SSE types, handednesses of connections between SSEs, coordinates of SSE starts and ends, types of interactions between SSEs and b-sheet definitions. For a user-defined structure pattern, ProSMoS lists all structures from a database that contain this pat- tern. ProSMoS server will be of interest to structural biologists who would like to analyze very general and distant structural similarities. The ProSMoS web server is available at: http://prodata.swmed. edu/ProSMoS/. INTRODUCTION Comparative methods advance our understanding of the relationship between structure and function in proteins (1). In comparative structure analysis, the most important and diﬃcult task is the detection of structural similarity, especially the discovery of remote but biologically mean- ingful connections between protein structures (2–4). Most of the structure comparison approaches assess the structure similarity by using superposition and closeness of either spatial coordinates or inter-residue contacts and ﬁnd sub-structures in common between protein structures (5,6). However, for the purpose of fold classiﬁcation it is more natural to look for speciﬁc 3D motifs or patterns instead of ﬁnding common features in two proteins (7,8). Protein folds are deﬁned by similarities in 3D packing of major SSEs, their spatial arrangement and topological connections, but without consideration of subtle diﬀer- ences in 3D coordinates(7). It is desirable to have a server that ﬁnds protein similarities using this deﬁnition. Pattern search, instead of a general structure similarity search, is more suited for this task. Namely, given a pat- tern of secondary structures with deﬁned topology and mutual arrangement in 3D, we would like to ﬁnd all struc- tures matching this pattern. Recently, we developed a pro- gram, Protein Structure Motif search (ProSMoS) to address this question (9). ProSMoS is not sensitive to ﬁner structure details, but ﬁnds proteins matching user- deﬁned structure pattern. Here, we describe a server based on ProSMoS. We convert 3D structure from each PDB ﬁle into 2D meta-matrix, which stores the type and length of SSEs and interactions between them. We oﬀer a set of rules for users to deﬁne the structure motif of inter- est by specifying query meta-matrix in which SSEs type, length, interaction type, handedness and information about b-sheets are customized by user. ProSMoS server carries out the pattern search for the query against a data- base [PDB or SCOP (10)] and reports structures matching the pattern. *To whom correspondence should be addressed. Tel: 214-645-5946; Fax: 214-645-5948; Email: grishin@chop.swmed.edu 2009 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.