Nucleic Acids Research, 2007, Vol. 35, Web Server issue W473–W476 doi:10.1093/nar/gkm423 PIC: Protein Interactions Calculator K. G. Tina, R. Bhadra and N. Srinivasan* Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012, India Received January 31, 2007; Revised April 17, 2007; Accepted May 9, 2007 ABSTRACT Interactions within a protein structure and interactions between proteins in an assembly are essential considerations in understanding molecular basis of stability and functions of proteins and their complexes. There are several weak and strong interactions that render stability to a protein struc- ture or an assembly. Protein Interactions Calculator (PIC) is a server which, given the coordinate set of 3D structure of a protein or an assembly, computes various interactions such as disulphide bonds, interactions between hydrophobic residues, ionic interactions, hydrogen bonds, aromatic– aromatic interactions, aromatic–sulphur interactions and cation–n interactions within a protein or between proteins in a complex. Interactions are calculated on the basis of standard, published criteria. The identified interactions between residues can be visualized using a RasMol and Jmol interface. The advantage with PIC server is the easy availability of inter-residue interaction calculations in a single site. It also determines the accessible surface area and residue-depth, which is the distance of a residue from the surface of the protein. User can also recognize specific kind of interactions, such as apolar–apolar residue interactions or ionic interac- tions, that are formed between buried or exposed residues or near the surface or deep inside. INTRODUCTION Analyses of atomic interactions in tertiary structures of proteins contribute richly to our understanding of sequence–structure relationships, structural basis of pro- tein stability and protein evolution. Studies on interac- tions between sidechains are commonly used in designing methods and identifying strategies for remote homology detection, protein fold recognition, protein structural comparisons and comparative protein modelling (1–6). For example, remote homology detection between pro- teins can rely on conservation of structural motifs involving interacting sidechains (1). Such studies also serve as guidelines in designing site-directed mutagenesis experiments (7) and in the understanding of the basis for residue conservation in homologous proteins (8). Interactions between subunits of multimeric proteins and interactions between interacting protein modules are also areas of intense study (9–13). Analyses on nature of sidechain–sidechain interactions across interacting inter- faces between protein modules have enlightened us on evolutionary conservation of protein–protein interactions and in distinguishing transient and permanent complexes (14–16). Diﬀerent kinds of interactions have been noted in the stabilization of tertiary structures, quaternary structures and assemblies of proteins. Roles and importance of interactions between apolar residues and hydrogen bonds are very well known (2). Importance of interactions such as aromatic–aromatic, aromatic–sulphur, cation–p and ionic interactions in the structure and function of proteins is also well realized (17–20). Observations and analyses of less common features such as exposed cluster of hydro- phobic residues, partially buried salt bridges and interac- tions of buried charged residues are also of speciﬁc interest (21–24) Here we report the development of a web-based service, PIC (Protein Interactions Calculator), to aid recognition and analyses of various kinds of interactions in tertiary structures of proteins and structures of protein–protein complexes. We have also integrated solvent accessibility calculations in PIC to aid recognition of interacting motifs that are exposed or buried. Further, the residue depth calculations are also made possible in PIC so that interactions deep inside the protein structure or near the surface can be recognized. Advantage of using residue depth parameter is that it can distinguish residues with no solvent accessible surface area in terms of how deep they are from the protein surface. MATERIALS AND METHODS Organization of PIC PIC server accepts atomic coordinate set of a protein structure in the standard Protein Data Bank (PDB) format. The user is prompted with selecting one or more of the following interaction types: Interaction between apolar residues, disulphide bridges, hydrogen bond *To whom correspondence should be addressed. Tel: +91 80 2293 2837; Fax: +91 80 2360 0535; Email: ns@mbu.iisc.ernet.in 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.