Disordered Motifs and Domains in Cell Control - October 11-15, 2014

Disordered Motifs and Domains in Cell Control

Sunday Speaker Abstracts

Computational Prediction of Protein-Peptide Binding Iris Antes , Manuel Glaser. Technical University of Munich, Freising, Germany.

Protein-peptide interactions are crucial for many important biological processes, especially in the context of signal transduction and protein-protein assembly. In addition, peptides also serve as natural inhibitors for proteins and therefore are often used as lead structures in pharmaceutical research. Prominent examples for peptide-based drugs are the inhibitors of viral proteases [1]. There exist very few computational approaches, which allow a structure-based prediction of protein-peptide binding, especially for larger peptides with more than 5 amino acids and surface- exposed binding sites. We have developed a two-stage method for this purpose: First, we predict the peptide’s binding site on the protein’s surface, which is important for many biologically relevant protein-peptide interactions for which the structure of the bound complex is not known. Second, we perform a throughout sampling of the peptide in the predicted binding site to identify the bound protein-peptide complex conformation using two methods: IRECS [2] and DynaDock [3], both allowing for an efficient description of the protein’s flexibility during protein-peptide assembly and thus fully flexible docking. The procedure was evaluated on a set of 20 different protein-peptide complexes and allows the successful prediction of bound protein-peptide complex structures (RMSD/exp. structure < 2.5 Â) for peptides with up to 16 amino acids starting from the unbound protein structure if available. The methodology was meanwhile successfully applied to predict Hsp70, TRAF2/6, and MHC peptide binding [4]. References: [1] Welsch C, Schweizer S, Shimakami T, Domingues FS, Kim S, Lemon, SM, Antes I. (2012), Antimicrob Agents Chemother 56: 1907-1915. [2] Hartmann C, Antes I, and Lengauer T (2009) Proteins, 74(3): 712-726. [3] Antes I (2010) Proteins 78(5): 1084-1104. [4] Marcinowski M, Seitz C, Rosam M, Elferich J, Behnke J, Bello C, Feige MJ, Becker CFW, Antes I, and Buchner J (2012) J. Mol. Biol, 425(3): 466-474.

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