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Inhibition of Pore Formation by Blocking the Assembly of Staphylococcus aureus α-Hemolysin Through a Novel Peptide Inhibitor: an In Silco Approach

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Abstract

Staphylococcus aureus self-assembling α-hemolysin heptamer is an acute virulence factor that determines the severity of S. aureus infections. Hence, inhibiting the heptamer formation is of considerable interest. However, both natural and chemical inhibitors reported so far has difficulties related to toxicity, bioavailability, and solubility, which necessitate in identifying some alternatives. Hence, in this study, potential peptides for α-hemolysin inhibition was developed using in silico based approach. Haddock server was used to understand the residues involved in complex formation. Based on the key residues involved in the interaction, 20 peptides were designed and docked with the α-hemolysin monomer (Chain A). Further, the best scored Chain A-peptide complex was chosen and docked with Chain B to identify the ability of dimer formation in the presence of designed peptide. The stability of the Chain A–B dimer, Chain A-peptide and Chain A-peptide-Chain B complex was studied by performing molecular dynamic simulation over 3,000 ps. The peptide IYGSKANRQTDK was found to be binding efficiently with Chain A of α-hemolysin with highest binding energy and also revealed that the designed peptide disturbed the dimer formation, which provided useful information in developing promising lead for inhibiting α-hemolysin assembly in the future.

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Acknowledgments

Saravanan Vijayakumar is supported by the DBT-BINC senior research fellowship.

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Authors and Affiliations

  1. Centre for Bioinformatics, School of Life Sciences, Pondicherry University, RV Nagar Kalapet, Pondicherry, 605014, India

    Nidhi Rani, V. Saravanan & P. T. V. Lakshmi

  2. Department of Biotechnology, School of Biotechnology and Health Sciences, Karunya University, Karunya Nagar, Coimbatore, Tamilnadu, India

    A. Annamalai

Authors
  1. Nidhi Rani
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  2. V. Saravanan
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  3. P. T. V. Lakshmi
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  4. A. Annamalai
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Correspondence to P. T. V. Lakshmi.

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Rani, N., Saravanan, V., Lakshmi, P.T.V. et al. Inhibition of Pore Formation by Blocking the Assembly of Staphylococcus aureus α-Hemolysin Through a Novel Peptide Inhibitor: an In Silco Approach. Int J Pept Res Ther 20, 575–583 (2014). https://doi.org/10.1007/s10989-014-9424-x

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  • DOI: https://doi.org/10.1007/s10989-014-9424-x

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