## 2 Results and Discussion
### Comparative test  
In terms of input and nature of results, the closest available relative of EpitopeMatch that we could find is Assam, though there are also clear differences, as e.g. Assam uses preprocessed data, whereas our code generates matches on the fly, which makes comparison of run-times misleading. Moreover, Assam uses the subgraph-isomorphism algorithm of [PERSON] [15] whereas EpitopeMatch uses a heuristic that iteratively builds up larger and larger matches. Nevertheless, both methods promise to identify discontinuous epitopes similar to a given query epitope in a database of structures. Hence, we have tested the performance of both algorithms by means of the same benchmark application. The test case is the search for epitopes that are similar to the maltose binding motif of the structure with PDB code 1 ANF in all structures of the PDB (55534 molecular structures as of February 3, 2009). We assume that Assam did operate on essentially the same version of the database, which is plausible given many matches found by both methods (see Supplementary Material). In the PDB there are several other maltose binding proteins with similar binding pockets that should be found by the queries. The search pattern was formulated as set of \(C_{\alpha}\) atoms and one atom representing each amino-acid side-chain (except for Glycine) of residues in the 5 A-neighborhood of the maltose ligand in 1 ANF. The full epitope comprised 17 atoms. We have submitted the epitope of 1 ANF to Assam via its web-service at [[http://grafss.imfr.net/assam/](http://grafss.imfr.net/assam/)]([http://grafss.imfr.net/assam/](http://grafss.imfr.net/assam/)) (the program used was actually called Aspres as of February 2, 2009, 18:17), and to EpitopeMatch. The latter was run on 16 cores of a Linux cluster (AMD Opteron 2218 2,6 GHz CPUs, each core with 4 GB RAM). Although the run times cannot be compared we give them here for completeness: Assam results were returned after 44h14m (for output see Supplementary Material), EpitopeMatch after 16h43m; because of the parallelization the total runtime of EpitopeMatch amounted to 267h20m. All 55534 PDB entries were screened for the epitope by EpitopeMatch for matches of 7 to 17 atoms with the query epitope and a maximum RMSD of 3 A. These conditions for minimum size of matches and maximum RMSD were in agreement with those reported by Assam. EpitopeMatch aborted in six cases of very large structures (2 CSE, 1 XI5, 1 XI4, 1 HTQ, 1N03, 1 MFR) because of too large memory requirements. In 47658 PDB entries subgraph matches were located, in 7870 entries no subgraph matches could be found by EpitopeMatch. Of all subgraphs the above conditions were fulfilled for a small subset: 119 such epitopes were identified by EpitopeMatch in 89 PDB structures, 60 epitopes were identified by Assam in 26 PDB structures (Figure 9; see also Supplementary Material). The set of Assam matches was a subset of those found by EpitopeMatch. Figure 9 reveals several remarkable differences between the results of the two methods. The set of full matches of 17 atoms identified by Assam is a subset of those found by EpitopeMatch, more precisely, EpitopeMatch finds full matches in three times as many proteins as Assam. The set of full or almost full matches includes rather clear cases as the maltose binding proteins 1 EZ9, 1 LAX, or  
Figure 8: Search for an epitope in a database [16]. 86 structures of different apo-enzymes are searched for a match with a ligand binding pocket of 45 amino-acids. The source of the query epitope (1 AKE) is included as control. The method identifies amongst the structures the one correct apo-structure (4 AKE) as match with lowest RMSD (“apo”). 1 MDP. 1 EZ9 is an interesting case since Assam finds matches of 8 and 9 atoms overlapping with the full binding motif, whereas EpitopeMatch finds a match of 10 atoms and a near-complete match of 16 atoms.