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Ab initio molecular simulations for proposing novel peptide inhibitors blocking the ligand-binding pocket of urokinase receptor

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Abstract

Recent biochemical experiments have revealed that a variety of proteases play important roles in cancer invasion and metastasis. Among these proteases, urokinase-type plasminogen activator (uPA) is particularly important, since its specific binding to the receptor (uPAR) existing on the surface of a cancer cell is considered to be a trigger for cancer invasion. It is thus expected that the blocking of the binding can inhibit cancer invasion in the cancer patients and improve their prognosis dramatically. To develop a potent inhibitor for the binding, many types of peptides of amino acids were produced and their effect on the cancer invasion was investigated in the previous biochemical experiments. On the other hand, our previous ab initio molecular simulations have clarified that some amino acid residues of uPA play important roles in the specific binding between uPA and uPAR. In the present study, we propose some peptides composed of these important residues and investigate the specific interactions and the binding affinity between uPAR and the peptides at an electronic level, using ab initio molecular simulations. Base on the results simulated, we elucidate which peptide can bind more strongly to uPAR and propose a novel potent peptide which can inhibit the binding between uPAR and uPA efficiently.

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Authors and Affiliations

  1. Department of Computer Science of Engineering, Toyohashi University of Technology, 1-1 Hibarigaoka, Tempaku-cho, Toyohashi, Aichi, 441-8580, Japan

    Tatsuroh Mizushima, Takuya Sugimoto, Tomoyo Kasumi, Kohta Araki & Noriyuki Kurita

  2. Department of Obstetrics and Gynecology, Nara Medical University, 840 Shijio-cho, Kashihara, Nara, 634-8521, Japan

    Hiroshi Kobayashi

Authors
  1. Tatsuroh Mizushima
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  2. Takuya Sugimoto
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  3. Tomoyo Kasumi
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  4. Kohta Araki
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  5. Hiroshi Kobayashi
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  6. Noriyuki Kurita
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Correspondence to Noriyuki Kurita.

Additional information

This paper belongs to Topical Collection 9th European Conference on Computational Chemistry (EuCo-CC9)

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Mizushima, T., Sugimoto, T., Kasumi, T. et al. Ab initio molecular simulations for proposing novel peptide inhibitors blocking the ligand-binding pocket of urokinase receptor. J Mol Model 20, 2292 (2014). https://doi.org/10.1007/s00894-014-2292-7

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  • DOI: https://doi.org/10.1007/s00894-014-2292-7

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