W474 Nucleic Acids Research, 2007, Vol. 35, Web Server issue between main chain atoms, hydrogen bond between main chain and sidechain atoms, hydrogen bond between two sidechain atoms, interaction between oppositely charged amino acids (ionic interactions), aromatic–aromatic inter- actions, aromatic–sulphur interactions and cation–p interactions. The input coordinate set is accepted, under each section of the page, for recognition of interactions within a polypeptide chain. If an ensemble of NMR- derived structures is input then the ﬁrst model in the ﬁle is taken as a representative and is used by the PIC server. The output corresponds to the list of residues involved in interaction type of interest. An option is provided, using RasMol (25) interface and Jmol interface, for enabling visualization of structure in the graphics with interactions highlighted. It is possible to get the results by e-mail. It is also possible to download the output ﬁles of the original programs. A separate panel is available for identiﬁcation of various types of interactions between polypeptide chains when a multi-chain PDB ﬁle is subjected to the analysis. All the said interactions could be explored for their occurrence across the inter-polypeptide chain interface. Thus this panel facilitates recognition of interactions between diﬀerent subunits in a multimeric protein structures or between proteins in a protein–protein complex structure. Figure 1 show ionic interactions between oppositely charged sidechains across the inter- face, formed between cyclin-dependent protein kinase and bound cyclin (26), recognized using PIC server. Solvent accessibility calculations could be used to identify diﬀerent kinds of interactions between buried or between solvent exposed residues. Solvent accessibility calculations are performed using NACCESS program (Hubbard, S.J. and Thornton, J.M., 1993, NACCESS Computer Program, Department of Biochemistry and Molecular Biology, University College London.). The exposed and buried residues are identiﬁed by 47% and 47% residue accessibility, respectively. Under this facility list of all the interaction types are displayed prompting the user to select list of interaction types of interest. For example, a user may prefer to identify interactions between apolar residues that are exposed. Figure 2 shows interactions between solvent exposed apolar resi- dues, in crambin (27), recognized using PIC server. Depth of an atom in a protein is deﬁned as the distance from the nearest atom in the surface of the protein structure. Mean depths of atoms of a residue deﬁnes the residue depth (28,29). Analogous to the panel on solvent accessibility, panel on residue depth enables the users to identify speciﬁc types of interactions near the protein surface or deep inside the core of the structure. Based on the analysis of residue depth parameter by Chakravarty and Varadarajan (28) we consider those residues with depths 45 A˚ as close to the protein surface and others as deep inside. Using this part of the PIC server it is possible to identify interactions between, say, aromatic residues near the protein structural surface. As calculation of residue depths takes a few minutes for most protein structures, results involving depth calculation are sent by e-mail to the user if a valid e-mail address is provided. Recognition of interactions Various types of interactions are recognized from the atomic coordinates using the standard criteria that are published. We used mainly the criteria suggested by NCI server (30) to identify non-canonical interactions in Figure 1. Interactions between oppositely charged amino acid side- chains in the interaction interface of cyclic dependent protein kinase 2 (CDKs) and cyclin identiﬁed using PIC server. The folds of CDK2 and cyclin and the charged residues in the interface formed by the two proteins are represented in diﬀerent colours. The ion pairs are highlighted by black dotted lines. This ﬁgure is produced using SETOR (35). Figure 2. Structure of crambin with solvent exposed and interacting apolar sidechains, recognized using PIC. Interactions between apolar sidechains is shown by green dots. Disulphide bonds are shown in yellow. This ﬁgure is produced using SETOR (35).