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Pharmaceutics 2018, 10(3), 72;

In Silico Structural Evaluation of Short Cationic Antimicrobial Peptides

School of Life and Medical Sciences, University of Hertfordshire, College Lane, Hatfield AL10 9AB, UK
UCL School of Pharmacy, University College London, 29/39 Brunswick Square, London WC1N 1AX, UK
Faculty of Pharmacy, University Business Academy, Trg mladenaca 5, 21000 Novi Sad, Serbia
NanoPuzzle Medicines Design, Business & Technology Centre, Bessemer Drive, Stevenage SG1 2DX, UK
Author to whom correspondence should be addressed.
Received: 18 May 2018 / Revised: 11 June 2018 / Accepted: 12 June 2018 / Published: 21 June 2018
(This article belongs to the Special Issue Protein Therapeutics)
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Cationic peptides with antimicrobial properties are ubiquitous in nature and have been studied for many years in an attempt to design novel antibiotics. However, very few molecules are used in the clinic so far, sometimes due to their complexity but, mostly, as a consequence of the unfavorable pharmacokinetic profile associated with peptides. The aim of this work is to investigate cationic peptides in order to identify common structural features which could be useful for the design of small peptides or peptido-mimetics with improved drug-like properties and activity against Gram negative bacteria. Two sets of cationic peptides (AMPs) with known antimicrobial activity have been investigated. The first reference set comprised molecules with experimentally-known conformations available in the protein databank (PDB), and the second one was composed of short peptides active against Gram negative bacteria but with no significant structural information available. The predicted structures of the peptides from the first set were in excellent agreement with those experimentally-observed, which allowed analysis of the structural features of the second group using computationally-derived conformations. The peptide conformations, either experimentally available or predicted, were clustered in an “all vs. all” fashion and the most populated clusters were then analyzed. It was confirmed that these peptides tend to assume an amphipathic conformation regardless of the environment. It was also observed that positively-charged amino acid residues can often be found next to aromatic residues. Finally, a protocol was evaluated for the investigation of the behavior of short cationic peptides in the presence of a membrane-like environment such as dodecylphosphocholine (DPC) micelles. The results presented herein introduce a promising approach to inform the design of novel short peptides with a potential antimicrobial activity. View Full-Text
Keywords: cationic antimicrobial peptides (AMPs); amphipathic conformation; molecular dynamics; protein structure prediction; dodecylphosphocholine (DPC) micelles cationic antimicrobial peptides (AMPs); amphipathic conformation; molecular dynamics; protein structure prediction; dodecylphosphocholine (DPC) micelles

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Passarini, I.; Rossiter, S.; Malkinson, J.; Zloh, M. In Silico Structural Evaluation of Short Cationic Antimicrobial Peptides. Pharmaceutics 2018, 10, 72.

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