Figure 1. Structure of Cy-3G and different Aβ polymorph. (a) Space-filling model of a simulated, single Aβ peptide solution structure. Positive and negative charges on the proteins are shown in tv_red and marine, respectively. The hydrophobic part is shown in light orange. (b) Space-filling model of a disease-relevant Aβ fibril structure. (c) Space-filling model of Cy-3G showing the positive charge (tv_red) and the hydrophobic character (light orange) on the 2-phenylbenzopyrylium core of this molecule.

Figure 1. Structure of Cy-3G and different Aβ polymorph. (a) Space-filling model of a simulated, single Aβ peptide solution structure. Positive and negative charges on the proteins are shown in tv_red and marine, respectively. The hydrophobic part is shown in light orange. (b) Space-filling model of a disease-relevant Aβ fibril structure. (c) Space-filling model of Cy-3G showing the positive charge (tv_red) and the hydrophobic character (light orange) on the 2-phenylbenzopyrylium core of this molecule.

Figure 2. The interaction between Cy-3G and the Aβ fibril. (a) The two binding sites between Cy-3G and a disease-relevant Aβ fibril. The cartoon representation is the Aβ fibril structure, and the pink stick presentation is the Cy-3G molecule. The first binding site is the hydrophobic core of one fibril stack, and the other binding site is on the opposite side of the hydrophobic site. (b,c) are the interaction details between Cy-3G and the first and second binding sites. The dashed lines represent hydrogen bonding, and amino acid residues involved in hydrophobic interactions were shown. For example, F4(E) indicates the fourth phenylalanine in Chain E of the Aβ fibril.

Figure 2. The interaction between Cy-3G and the Aβ fibril. (a) The two binding sites between Cy-3G and a disease-relevant Aβ fibril. The cartoon representation is the Aβ fibril structure, and the pink stick presentation is the Cy-3G molecule. The first binding site is the hydrophobic core of one fibril stack, and the other binding site is on the opposite side of the hydrophobic site. (b,c) are the interaction details between Cy-3G and the first and second binding sites. The dashed lines represent hydrogen bonding, and amino acid residues involved in hydrophobic interactions were shown. For example, F4(E) indicates the fourth phenylalanine in Chain E of the Aβ fibril.

Figure 3. Detailed interaction between Cy-3G and an Aβ peptide. (a) The binding site between Cy-3G and an Aβ peptide. The slate carton representation is the Aβ peptide solution structure, and the pink stick presents Cy-3G. (b) The interaction details between Cy-3G and the Aβ peptide. The dashed lines represent hydrogen bonding, and amino acid residues involved in hydrophobic interactions were shown.

Figure 3. Detailed interaction between Cy-3G and an Aβ peptide. (a) The binding site between Cy-3G and an Aβ peptide. The slate carton representation is the Aβ peptide solution structure, and the pink stick presents Cy-3G. (b) The interaction details between Cy-3G and the Aβ peptide. The dashed lines represent hydrogen bonding, and amino acid residues involved in hydrophobic interactions were shown.

Table 1. Binding parameters of Cy-3G to different Aβ polymorphs.

Table 1. Binding parameters of Cy-3G to different Aβ polymorphs.

Aβ PolymorphCDOCKER
Interaction Energy
(kJ/mol)Number of Hydrogen BondsNumber of Amino Acid Residues Involved in Hydrophobic Interactions Single peptide−43.29411Fibril site1−181.3149Fibril site2−197.7247