Molecular Docking of Monomethine Cyanine Dyes to Lysozyme Amyloid Fibrils

Abstract

Protein aggregation into highly ordered supramolecular aggregates is the hallmark of many degenerative diseases including the neurological disorders (Parkinson’s, Alzheimer’s, and Huntington’s diseases), type II diabetes, systemic amyloidosis, spongiform encephalopathies, etc. One of the simplest and effective methods for the identification and characterization of amyloid fibrils in vitro and the visualization of amyloid inclusions in vivo is based on the use of probes sensitive to the beta-pleated motifs. In the attempt to design new amyloid-sensing dyes or to optimization the existing molecules, it is crucial to have the sufficient knowledge of the molecular and atomic levels interactions in the binding sites. Among the especially useful methods available to provide the atomic-level insights into the mechanisms of various types of biomolecular interactions is molecular docking technique. In the present study, the molecular docking tool has been employed to investigate the interactions between the monomethine cyanine dyes and the lysozyme amyloid fibrils constructed from the K-peptide of lysozyme, GILQINSRW (residues 54–62 of the wild-type protein). Using the AutoDOCK and the protein-ligand interaction profiler PLIP it was found: i) monomethines interact with the fibril surface (with the aromatic residues on the top of β-sheet or with the edges of the β-sheet); ii) the dye binding is governed by the hydrophobic interactions, salt bridges and the hydrogen bonds between the aliphatic substituents on the nitrogen atom of benzothiazole part of dye molecules and the lysozyme amyloid fibril; iii) the variations in the cyanine structure and in the lysozyme amiloid twisting didn’t insert significant effect on the binding mode of cyanines.