Computational assessment of amino acid-coupled benzanthrone 2-aminoacetamides as molecular probes for insulin amyloid fibril visualization

Abstract

Fluorescent proteins are currently the most extensively studied fluorescent markers used in bio-imaging, and many such fluorescent markers are used in research to label amino acids and proteins. However, developing suitable fluorescent probes to label peptides and proteins remains a major challenge. In this context, the twelve recently reported amino acid-coupled benzanthrone 2-aminoacetamide molecules (BA1–BA12) attracted our attention and we screened their intense luminescence properties computationally for bio-visualization applications. DFT calculations in the gas and solvent phases indicated the presence of N–H⋯O hydrogen bond interactions that stabilize the BA3, BA5, BA9, BA4, BA7 and BA12 molecules in the ground state. Electronic spectral studies reveal that these molecules have high Stokes shifts, which implies that they are excellent for bio-visualization applications. The sensing properties of these molecules are evaluated through molecular docking and 100 ns molecular dynamics simulations. These molecules are stabilized in the binding pockets of insulin amyloid fibrils and can easily dissociate from these fibrils after 50 ns. We believe that this research will be valuable in assisting researchers to design more efficient molecules for bio-imaging applications, addressing the ongoing need for suitable fluorescent probes for the labelling of peptides and proteins.