Side chain substitution benchmark for peptide/MHC interaction

Abstract
The prediction of T-cell epitopes is an essential part in virtual immunology. Apart from sequence-based techniques, which achieve good results but fail to give insight into the binding behavior of a certain peptide binding to a major histocompatibility complex, structure-based approaches are another important technique. An essential step is the correct placement of the side chains for a given peptide in cases where no experimental data for the structure are available. To our knowledge, no benchmark for side chain substitution in the area of HLA has been reported in the literature. Here, we present a comparison of five different tools (SCWRL, SCATD, SPDBV, SCit, IRECS) applicable for side chain substitution. Each tool is tested on 29 different HLA-A2 structures with experimentally known side chain positions. Parts of the benchmark are correctness, reliability, runtime, and usability. For validation, the root mean square deviations between X-ray structures and predicted structures are used. All tools show different strengths and weaknesses.