BLIND AND FLEXIBLE PEPTIDE-PROTEIN DOCKING

Michal Slutzki 1,2 Avraham Ben-Shimon 1,2 Lizi Hazan 1,2 Masha Niv 1,2
1The Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot
2The Fritz Haber Center for Molecular Dynamics, The Hebrew University of Jerusalem, Jerusalem

Due to increasing interest in peptides as signaling modulators and drug candidates(Rubinstein & Niv, 2009), several methods for peptide docking to their target proteins are being actively developed (Slutzki et al, in preparation).

AnchorDock protocol(Ben-Shimon & Niv) was developed in our lab to perform a blind (without prior knowledge of the binding site) and flexible docking of peptides to their target protein. Based on simulated annealing molecular dynamics simulations of a pre-folded free peptide conformation to precomputed anchoring spots detected on the protein surface, it is able to make a prediction of binding to unbound conformation of the target protein(Ben-Shimon & Niv, Chapnik et al., 2014), by narrowing search to the most relevant parts of the conformational space.

Using a set of protein-peptide complexes, where the protein partner is available both in bound and unbound states, we compare AnchorDock performance to recently published blind docking servers and explore the role of peptide pre-folding in solution for the quality of results.

Opportunities and challenges in studying GPCR-peptide interactions are discussed and mapping of GPCR-peptide sites are presented.

Ben-Shimon, A. & Niv, Masha Y. Structure 23, 929-940.

Chapnik, N., Genzer, Y., Ben-Shimon, A., Niv, M. Y. & Froy, O. (2014). J Endocrinol 221, 89-99.

Rubinstein, M. & Niv, M. Y. (2009). Biopolymers 91, 505-513.









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