Amino Acids

, Volume 47, Issue 3, pp 543–559 | Cite as

Structural analysis of membrane-bound hECE-1 dimer using molecular modeling techniques: insights into conformational changes and Aβ1–42 peptide binding

  • Kailas D. SonawaneEmail author
  • Sagar H. Barage
Original Article


The human endothelin converting enzyme-1 (hECE-1) is a homodimer linked by a single disulfide bridge and has been identified as an important target for Alzheimer’s disease. Structural analysis of hECE-1 dimer could lead to design specific and effective therapies against Alzheimer’s disease. Hence, in the present study homology model of transmembrane helix has been constructed and patched with available crystal structure of hECE-1 monomer. Then, membrane-bound whole model of hECE-1 dimer has been developed by considering biophysical properties of membrane proteins. The explicit molecular dynamics simulation revealed that the hECE-1 dimer exhibits conformational restrains and controls total central cavity by regulating the degree of fluctuations in some residues (238–226) for substrate/product entrance/exit sites. In turn, conformational rearrangements of interdomain linkers as well as helices close to the inner surface are responsible for increasing total central cavity of hECE-1 dimer. Further, the model of hECE-1 dimer was docked with Aβ1–42 followed by MD simulation to investigate possible orientation and interactions of Aβ1–42 in catalytic groove of hECE-1 dimer. The free energy calculations exposed the stability of complex and helped us to identify key residues of hECE-1 involved in interactions with Aβ1–42 peptide. Hence, the present study might be useful to understand structural significance of membrane-bound dimeric hECE-1 to design therapies against Alzheimer’s disease.


Human endothelin converting enzyme (hECE-1) Homology modeling MD simulation Molecular docking 1–42 peptide 



KDS gratefully acknowledges the University Grand Commission, New Delhi for financial support under the UGC major research project. The authors are very much thankful to Computer Centre, Shivaji University, Kolhapur for providing computational facility.

Conflict of interest

All authors have no conflict of interest.

Supplementary material

726_2014_1887_MOESM1_ESM.docx (3.5 mb)
Supplementary material 1 (DOCX 3595 kb)

Supplementary material 2 (WMV 2403 kb)


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Copyright information

© Springer-Verlag Wien 2014

Authors and Affiliations

  1. 1.Structural Bioinformatics Unit, Department of BiochemistryShivaji UniversityKolhapurIndia
  2. 2.Department of BiotechnologyShivaji UniversityKolhapurIndia

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