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Hydrogen bonds in anoplin peptides aid in identification of a structurally stable therapeutic drug scaffold

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Abstract

Multi-drug resistance is a major issue faced by the global pharmaceutical industry. Short antimicrobial peptides such as anoplins can be used to replace antibiotics, thus mitigating this issue. Antimicrobial activity, non-toxicity, and structural stability are essential features of a therapeutic drug. Antimicrobial activity and toxicity to human erythrocytes have been previously reported for anoplin and anoplin R5K T8W. This study attempts to identify a therapeutic peptide drug scaffold between these peptides by examining their structural stability, mainly based on the hydrogen bonds (H-bond) found in their structures. The static structure of anoplin R5K T8W displayed lower H-bond distances than anoplin, thereby exhibiting enhanced structural stability. Dynamic stability studies revealed that conformers of anoplin R5K T8W exhibited lower hydrogen bond distances (HBDs), higher H-bond occupancies, and higher radial distribution function (RDF) of H-bonds in comparison with conformers of anoplin. Furthermore, conformers of anoplin R5K T8W generated using 50-ns molecular dynamics simulation displayed lower conformational free energy than anoplin, thus establishing its higher structural stability. Overall, anoplin R5K T8W can be claimed as a promising scaffold that may be used for therapeutic purposes. In conclusion, H-bonds play a major role in structural stability and may aid in identification of a therapeutic peptide scaffold.

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Acknowledgments

The authors thank Vellore Institute of Technology (Deemed to be University) for providing “VIT SEED GRANT” for carrying out this research work.

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Data other than supplementary data will be made available on request.

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  1. Department of Biotechnology, School of Biosciences and Technology, Vellore Institute of Technology (Deemed to be University), Vellore, Tamil Nadu, 632014, India

    Shruti Sunil Ranade & Rajasekaran Ramalingam

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Conceptualization: Shruti Sunil Ranade; methodology: Shruti Sunil Ranade; formal analysis and investigation: Shruti Sunil Ranade; writing—original draft preparation: Shruti Sunil Ranade; writing—review and editing: Rajasekaran Ramalingam; funding acquisition: Rajasekaran Ramalingam; resources: Rajasekaran Ramalingam; supervision: Rajasekaran Ramalingam.

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Correspondence to Rajasekaran Ramalingam.

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Ranade, S.S., Ramalingam, R. Hydrogen bonds in anoplin peptides aid in identification of a structurally stable therapeutic drug scaffold. J Mol Model 26, 155 (2020). https://doi.org/10.1007/s00894-020-04380-x

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