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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