In Silico Structural Evaluation of Short Cationic Antimicrobial Peptides
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 pharm...
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doaj-1d16e6ebcdba4df08832e8d5811e9cd72020-11-25T00:57:19ZengMDPI AGPharmaceutics1999-49232018-06-011037210.3390/pharmaceutics10030072pharmaceutics10030072In Silico Structural Evaluation of Short Cationic Antimicrobial PeptidesIlaria Passarini0Sharon Rossiter1John Malkinson2Mire Zloh3School of Life and Medical Sciences, University of Hertfordshire, College Lane, Hatfield AL10 9AB, UKSchool of Life and Medical Sciences, University of Hertfordshire, College Lane, Hatfield AL10 9AB, UKUCL School of Pharmacy, University College London, 29/39 Brunswick Square, London WC1N 1AX, UKSchool of Life and Medical Sciences, University of Hertfordshire, College Lane, Hatfield AL10 9AB, UKCationic 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.http://www.mdpi.com/1999-4923/10/3/72cationic antimicrobial peptides (AMPs)amphipathic conformationmolecular dynamicsprotein structure predictiondodecylphosphocholine (DPC) micelles |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ilaria Passarini Sharon Rossiter John Malkinson Mire Zloh |
spellingShingle |
Ilaria Passarini Sharon Rossiter John Malkinson Mire Zloh In Silico Structural Evaluation of Short Cationic Antimicrobial Peptides Pharmaceutics cationic antimicrobial peptides (AMPs) amphipathic conformation molecular dynamics protein structure prediction dodecylphosphocholine (DPC) micelles |
author_facet |
Ilaria Passarini Sharon Rossiter John Malkinson Mire Zloh |
author_sort |
Ilaria Passarini |
title |
In Silico Structural Evaluation of Short Cationic Antimicrobial Peptides |
title_short |
In Silico Structural Evaluation of Short Cationic Antimicrobial Peptides |
title_full |
In Silico Structural Evaluation of Short Cationic Antimicrobial Peptides |
title_fullStr |
In Silico Structural Evaluation of Short Cationic Antimicrobial Peptides |
title_full_unstemmed |
In Silico Structural Evaluation of Short Cationic Antimicrobial Peptides |
title_sort |
in silico structural evaluation of short cationic antimicrobial peptides |
publisher |
MDPI AG |
series |
Pharmaceutics |
issn |
1999-4923 |
publishDate |
2018-06-01 |
description |
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. |
topic |
cationic antimicrobial peptides (AMPs) amphipathic conformation molecular dynamics protein structure prediction dodecylphosphocholine (DPC) micelles |
url |
http://www.mdpi.com/1999-4923/10/3/72 |
work_keys_str_mv |
AT ilariapassarini insilicostructuralevaluationofshortcationicantimicrobialpeptides AT sharonrossiter insilicostructuralevaluationofshortcationicantimicrobialpeptides AT johnmalkinson insilicostructuralevaluationofshortcationicantimicrobialpeptides AT mirezloh insilicostructuralevaluationofshortcationicantimicrobialpeptides |
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