Insights into binding modes of tumstatin peptide T7 with the active site of α_vβ₃ integrin

Abstract

Through interaction with the active site of α_vβ₃ integrin, tumstatin T7 peptide inhibits both the angiogenesis and the proliferation of tumour cells. In this work, docking in conjunction with molecular dynamics simulation was used to explore the binding mode of T7 peptide and α_vβ₃ integrin. The binding mode analysis revealed that the residues Ser⁹⁰, Arg⁹¹, Asp⁹³ and Tyr⁹⁴ in T7 peptide, and (α)-Asp¹⁵⁰, (β)-Arg²¹⁴, (α)-Asp¹⁴⁸ (α)-Gln²¹⁴ and (α)-Glu¹²³ in the active site of α_vβ₃ integrin were most likely the key interaction sites. The hydroxyl of Tyr⁹⁴ coordinates α_vβ₃ via a Mn²⁺ ion, revealing that Mn²⁺ is also an important factor for the interaction. The insight into these key interaction sites not only suggests that the active site of α_vβ₃ integrin can bind to molecules through multiple binding mechanisms, but also provides some useful information for structure-based drug design.

Keywords:

• T7 peptide
• α_vβ₃ integrin
• docking
• MD simulation
• MM/GBSA

Acknowledgements

This work is supported by the exploration fund ST1119 and development fund SF1004 from the Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College. We thank the HPCC of PUMC for providing the use of the software MOE v2008.10 and AMBER 10. We also thank Desou Song (Laboratory of Insect Toxicology and Key Laboratory of Natural Pesticide and Chemical Biology, Ministry of Education, South China Agricultural University, Guangzhou 510462, China) for the help of calculating the free energy.

Notes

1. These authors contributed equally to this work.

Additional information

Notes on contributors

Jinhang Zan

1

Xin He

1