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Identification of Angiotensin Converting Enzyme Inhibitor: An In Silico Perspective

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Abstract

Angiotensin Converting Enzyme (ACE) regulates blood pressure and electrolyte balance by converting angiotensin I into angiotensin II, which acts as vasoconstrictor and aldosterone-stimulating peptide. ACE is also known to inactivate vasodilators, bradykinin and angiotensin 1–7 peptide. Thus, the down-regulation of ACE activity would be very beneficial in various cardiovascular diseases. In present in silico approach, virtual screening was performed to identify possible novel inhibitors of testis ACE (tACE) from ZINC database using Dockblaster. All screened compounds were filtered through Lipinski’s rules and other properties. PyRx tool was then implemented to dock selected compounds. Finally, ligand ZINC48251687 re-docked using Autodock 4.2 with His 383, His 387 and Glu 411 as flexible residues of tACE. Molecular Dynamics simulation was then carried out to investigate the binding stability of the screened ligand in a dynamic environment. It has been observed that tACE-ligand complex was quite stable over the entire simulation run. We found that ligand was stabilized by strong hydrogen bonding interactions with Ala 354, Ala 356, Tyr 523 and Zn2+ of tACE. Thus, ZINC48251687 could be used as starting point for the development of new non-peptidic inhibitor of tACE and for designing drug against cardiovascular and related renal diseases.

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Acknowledgments

CBJ is thankful to Shivaji University, Kolhapur for providing fellowship in the form of Golden Jubilee Research Fellowship. MJD is gratefully acknowledged to Department of Science and Technology, New Delhi for providing fellowship as research assistance under the scheme Promotion of University Research and Scientific Excellence (DST-PURSE). KDS is thankful to University Grants Commission, New Delhi for providing research Grants. Authors are thankful to Computer Centre, Shivaji University, Kolhapur for providing computational facility.

Conflict of interest

Chidambar Jalkute, Sagar Barage, Maruti Dhanavade and Kailas Sonawane declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Structural Bioinformatics Unit, Department of Biochemistry, Shivaji University, Kolhapur, Maharashtra (M.S.), 416004, India

    Kailas D. Sonawane

  2. Department of Microbiology, Shivaji University, Kolhapur, Maharashtra (M.S.), 416004, India

    Chidambar B. Jalkute, Maruti J. Dhanavade & Kailas D. Sonawane

  3. Department of Biotechnology, Shivaji University, Kolhapur, Maharashtra (M.S.), 416004, India

    Sagar H. Barage

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  1. Chidambar B. Jalkute
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  2. Sagar H. Barage
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  3. Maruti J. Dhanavade
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  4. Kailas D. Sonawane
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Correspondence to Kailas D. Sonawane.

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Jalkute, C.B., Barage, S.H., Dhanavade, M.J. et al. Identification of Angiotensin Converting Enzyme Inhibitor: An In Silico Perspective. Int J Pept Res Ther 21, 107–115 (2015). https://doi.org/10.1007/s10989-014-9434-8

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  • DOI: https://doi.org/10.1007/s10989-014-9434-8

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