Table 1. α-syn binding of ligands in figures 1, 2 in aqueous solution observed in MD simulations.

DOP and its oxidation derivatives abbreviations are explained in detail in figure 1. Column titles from left to right: (i) ligand name (ii) percentage of time in which the ligands are bound to α-syn and (iii) to the ¹²⁵YEMPS¹²⁹ ‘target’ region, (iv-v) stabilizing electrostatic interaction energies between the ligands and E83 and E61, two negatively charged residues of the NAC region. Energy values of the force field are very approximate¹ and do not take into account the screening of the solvent. They should be taken here only for qualitative comparisons. Here they are normalized with respect to the most negative interaction energy between the neutral ligands and the two negative residues (-2.8 kcal/mol, relative to the interaction between IQ and E83). The DOPH/E61 energy turns out to be very large in absolute value because the ligand is charged, in contrast to all the others.

Ligand	% protein	% target	Point Charge Model Av ± Std (E83)	Point Charge Model Av ± Std (E61)
DOPH	70	32	0.0	−14.9
DOP	69	46	0.0	−0.7
DQ	49	28	−0.3	−0.3
DCH	72	32	−0.8	−0.5
DHI	91	16	0.0	0.0
IQ	62	32	−1.0	−0.3
6-aminoindole	68	23	0.0	0.0
Tyramine	48	19	0.0	0.1
4-(2-aminoethyl) aniline	39	9	0.0	-0.2
5-hydroxyindole	70	23	-0.9	0.0
2-amino-4-tert-butylphenol	62	19	0.0	0.0

¹L. Guidoni, V. Torre and P. Carloni, FEBS Letters 477 (2000) 37-42.