Journal of the Iranian Chemical Society

, Volume 14, Issue 9, pp 2023–2039 | Cite as

Are Pro8/Pro18 really critical for functional dynamic behavior of human endostatin N-terminal peptide? A comparative molecular dynamics study

  • Hassan Rasouli
  • Masomeh Mehrabi
  • Seyed Shahriar ArabEmail author
  • Reza KhodarahmiEmail author
Original Paper


Endostatin which is derived from the non-collagenous domain 1 of collagen XVIII and is a recently identified broad spectrum anti-angiogenesis agent, inhibits 65 different tumor types. The N-terminal fragment of endostatin protein (ES) has the same antitumor, antimigration and antipermeability effects as the entire protein. In the current study, we modeled two mutant variants of ES with two mutation sites (M1-ES (Pro8 → Ala) and M2-ES (Pro18 → Ala)) and tried to understand proline’s effect on the peptide structure/stability by introducing P8A/P18A mutations, and then in order to gain functional insight into mutation caused by amino acid substitution to the peptide structure/function, these effects were predicted using computational tools. From the RMSD analyses, it can be concluded that dynamic behavior of wild-type and mutant structures was not significantly different from each other and all systems reached equilibrium. The RMSF analysis also revealed that the M2-ES has smaller overall flexibility than the WT-ES and M1-ES structures. The radius of gyration analysis then confirmed the structure of M2-ES compared to wild-type and M1 variant becomes more compact during simulation of our systems. Finally, molecular dynamics simulation analysis shows that replacement of Pro residue with Ala is able to induce a distinct β-sheet in both mutant structures. Indeed, the docking analysis shows the WT-ES and M2-ES bind to the same region of αvβ3 integrin, suggesting similar interaction pattern with a relatively equal binding energy into this receptor. Our results speculated that the P8A/P18A replacements confer no improvement (or no tangible weakness) in the peptide biological activity although is able to change structural conformation of N-terminal fragment of human endostatin protein.


Proline Endostatin MD simulation Molecular docking 



We thank the Research Council of Kermanshah University of Medical Sciences (KUMS) for financial support of this investigation (Grant No. 95303). We specially thank Mrs. Shirin Valizadeh for her gracious helps in the time of reviewing and revising of this article. Effective, instructive and invaluable comments provided by the respectful editor and anonymous reviewers are gratefully acknowledged.

Compliance with ethical standards

Conflict of interest

Authors certify that no actual or potential conflict of interest in relation to this article exists.


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Copyright information

© Iranian Chemical Society 2017

Authors and Affiliations

  1. 1.Medical Biology Research CenterKermanshah University of Medical SciencesKermanshahIran
  2. 2.Department of Biophysics, Faculty of Biological SciencesTarbiat Modares UniversityTehranIran
  3. 3.Department of Pharmacognosy and Biotechnology, Faculty of PharmacyKermanshah University of Medical SciencesKermanshahIran

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