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Biotechnology Letters

, Volume 39, Issue 12, pp 1843–1851 | Cite as

Dynamics of allosteric modulation of lymphocyte function associated antigen-1 closure-open switch: unveiling the structural mechanisms associated with outside-in signaling activation

  • Maryam Abdullahi
  • Fisayo A. Olotu
  • Mahmoud E. Soliman
Original Research Paper

Abstract

Objectives

To provide insight into the dynamics of the shape-shifting mechanistic events associated with the opening (activation) of Lymphocyte Function Associated Antigen-1 upon allosteric modulation by an activator, ICAM Binding Enhancer-667 (IBE-667), using molecular dynamics simulation.

Results

Various parameters were used to appropriately describe and understand the sequence of events that characterized its activation across the simulation period such as residual distances, TriCα angles; as well as the dihedral angle. Our findings revealed a significant residual fluctuation and stability difference between both systems. Also, there was a synergistic coordination of the active MIDAS site by the downward pull of the α7 helix upon ligand binding, which appeared to be directly proportional to each other.

Conclusion

Allosteric binding of IBE-667, activated LFA-1 integrin as evidenced by residual motion at the MIDAS region which appears to be synergistically coordinated by the downward pull of the α7 helix.

Keywords

Allosteric Integrin lymphocyte function associated antigen-1 Modulation Molecular dynamics Synergistic 

Notes

Acknowledgement

The authors acknowledge the School of Health Sciences, University of KwaZulu Natal, Westville Campus for financial support and Centre of High Performance Computing (www.chpc.ac.za), Cape Town, RSA, for computational resources.

Compliance with ethical standards

Conflict of interest

Authors declare no conflict of interest.

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Copyright information

© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  • Maryam Abdullahi
    • 1
  • Fisayo A. Olotu
    • 1
  • Mahmoud E. Soliman
    • 1
    • 2
    • 3
  1. 1.Molecular Modeling and Drug Design Research, Group School of Health SciencesUniversity of KwaZulu- NatalDurbanSouth Africa
  2. 2.College of Pharmacy and Pharmaceutical SciencesFlorida Agricultural and Mechanical University (FAMU)TallahasseeUSA
  3. 3.Department of Pharmaceutical Organic Chemistry Faculty of PharmacyZagazig UniversityZagazigEgypt

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