Charges' interaction in polyelectrolyte (nano)complexing of His6-OPH with peptides: Unpredictable results due to imperfect or useless concept?

Int J Biol Macromol. 2019 Nov 1:140:368-376. doi: 10.1016/j.ijbiomac.2019.08.137. Epub 2019 Aug 16.

Abstract

Quorum Quenching (QQ) enzymes can be used to prevent bacterial antibiotic resistance by degradation of Quorum Sensing (QS) signaling molecules, for example N-acyl homoserine lactones (AHLs). This paper is aimed at the in silico investigation of the possible combinations of hexahistidine-tagged organophosphorus hydrolase (His6-OPH) with antimicrobial peptides (AMPs) to improve the enzyme activity and, promisingly, stability. This shall help creating a nanosized QQ preparation capable to hydrolyze different AHLs and possessing an antimicrobial activity. To achieve this, binding of AMPs and His6-OPH was simulated by molecular docking, and various interaction parameters (affinity, charge, contact area, etc.) of the generated models were studied. Both anionic and cationic polypeptides were shown to bind to His6-OPH with negligible effect of their charge, that significantly deviates from the charge-to-charge interaction concept. The (nano)complexes of His6-OPH with Indolicidin and Temporin A appear to have the most balanced characteristics which were issued experimentally also.

Keywords: Antimicrobial peptide; Hexahistidine-tagged organophosphorus hydrolase; Molecular docking.

MeSH terms

  • Acyl-Butyrolactones / metabolism
  • Anti-Bacterial Agents / chemistry*
  • Antimicrobial Cationic Peptides / chemistry
  • Aryldialkylphosphatase / chemistry*
  • Histidine / chemistry*
  • Hydrolysis
  • Models, Molecular
  • Molecular Docking Simulation*
  • Nanocomposites / chemistry
  • Oligopeptides / chemistry*
  • Peptides / chemistry*
  • Polyelectrolytes / chemistry*
  • Proteins / chemistry
  • Quorum Sensing*

Substances

  • Acyl-Butyrolactones
  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • His-His-His-His-His-His
  • Oligopeptides
  • Peptides
  • Polyelectrolytes
  • Proteins
  • temporin
  • indolicidin
  • Histidine
  • Aryldialkylphosphatase