Conférence NARC

Prof. I ANTES will present " Computational prediction of protein-peptide binding", M. Glaser, S. Hecht, and I. Antes

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, 3] and DynaDock [4], both allowing for an efficient description of the protein’s flexibility during protein-peptide assembly and thus fully flexible docking.
The procedure was successfully evaluated on a set of divers protein-peptide complexes and allows the successful prediction of bound protein-peptide complex structures (RMSD < 2.5 A) 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, EF-Tu, and PDI peptide binding [5-7].

References:
[1]Welsch C, et al. (2012) Antimicrob Agents Chemother 56: 1907-1915.
[2]Hartmann C, Antes I, and Lengauer T (2007) Protein Science, 16(7): 1294-1307.
[3]Hartmann C, Antes I, and Lengauer T (2009) Proteins, 74(3): 712-726.
[4] Antes I (2010) Proteins 78(5): 1084-1104.
[5] Marcinowski M, et al. (2012) J. Mol. Biol,
425(3): 466-474.
[6]Gross S, et al. (2013) ChemMedChem, 8(12): 1954-1962.
[7]Eirich J, et al. (2014) Angew Chem Int Ed Engl, 53(47): 12960-12965.

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