Published online 22 May 2009 Nucleic Acids Research, 2009, Vol. 37, Web Server issue W565–W570 doi:10.1093/nar/gkp405 MolLoc: a web tool for the local structural alignment of molecular surfaces Stefano Angaran 1 , Mary Ellen Bock 2 , Claudio Garutti1,* and Concettina Guerra1,3 1Department of Information Engineering, University of Padova, Via Gradenigo 6a, Padova, Italy, 2Department of Statistics, Purdue University 250 N. University Street, West Lafayette, IN 47907-2066 and 3College of Computing, Georgia Institute of Technology, Atlanta, GA 30332-0280, USA Received February 28, 2009; Revised April 20, 2009; Accepted May 2, 2009 ABSTRACT MolLoc stands for Molecular Local surface compar- ison, and is a web server for the structural compar- ison of molecular surfaces. Given two structures in PDB format, the user can compare their binding sites, cavities or any arbitrary residue selection. Moreover, the web server allows the comparison of a query structure with a list of structures. Each comparison produces a structural alignment that maximizes the extension of the superimposition of the surfaces, and returns the pairs of atoms with similar physicochemical properties that are close in space after the superimposition. Based on this subset of atoms sharing similar physicochemical properties a new rototranslation is derived that best superimposes them. MolLoc approach is both local and surface-oriented, and therefore it can be particularly useful when testing if molecules with different sequences and folds share any local sur- face similarity. The MolLoc web server is available at http://bcb.dei.unipd.it/MolLoc. INTRODUCTION Structural comparison is used extensively to determine the function of proteins, and to study the interactions between proteins and nucleic acids. Most of the tools currently available are for global structural comparison. For instance, SSAP (1), STRUCTAL (2), DALI (3), LSQMAN (4), CE (5) and SSM (6) ﬁnd the rototransla- tion of two given structures that maximizes the number of residues that are close after the global alignment (7). Moreover, the molecule is often represented by its atoms or a subset of its atoms (e.g. Ca atoms), which is a simpli- ﬁed representation of the molecular structure. In this article, we introduce MolLoc (Molecular Local), a web server for the recognition of similar regions on molecular surfaces. The surfaces may be restricted to cav- ities, binding sites or any residue selection of complete protein, RNA or DNA. The server determines the most extended similar regions of the selected surfaces. This application can be particularly useful when the user is interested in inferring functional information for a mole- cule, be it a protein, RNA or DNA. First, if the molecule has a binding site, the surface comparison of its binding site with binding sites of other molecules can identify potential ligands or inhibitors to use within its binding site. Second, if the molecule has no known binding sites but has a set of functionally relevant residues, the com- parison of these residues with other binding sites can sug- gest new ligands for these residues. Third, if the molecule has no functional characterization at all, comparing its cavities with other binding sites can provide clues to the molecular function, since binding sites usually lie in cav- ities (8,9). Available tools that provide related facilities are Multibind (10), 3D-surfer (11), eF-seek (12) and FunClust (13). Multibind (http://bioinfo3d.cs.tau.ac.il/ MultiBind/) recognizes spatial chemical binding patterns common to a set of protein structures. It handles several proteins at once but, like eF-seek (http://ef-site.hgc.jp/eF- seek/index.jsp), aligns binding sites only. 3D-surfer (http://dragon.bio.purdue.edu/3d-surfer/) performs a comparison of a query protein surface against all protein structures in the PDB and retrieves those with highest global surface similarity with the query. It establishes global surfaces similarity but, unlike MolLoc, does not search for local surface regions corresponding to candi- date binding sites. FunClust (http://pdbfun.uniroma2.it/ funclust/) takes as input a list of proteins and identiﬁes a set of shared residues. It matches proteins based on a local structural representation, not on surface information as in MolLoc. MATERIALS AND METHODS Input data MolLoc can perform pairwise surface comparison of two structures, or multiple pairwise surface comparison of a query structure with a list of structures (Figure 1). *To whom correspondence should be addressed. Tel: +39 049 827 7928; Fax: +39 049 827 7799; Email: garuttic@dei.unipd.it 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.