Electronic Supplementary Material For s2

Electronic Supplementary Material for

Computational analysis of the binding ability of heteroyclic and conformationally constrained epibatidine analogues in the neuronal nicotinic acetylcholine receptor

Elena Soriano, José Marco-Contelles, Inés Colmena, Luis Gandía In Figure 1, a schematic picture of the complex between epibatidine and the AChBP receptor (PDB code 2BYQ) [Bourne Y, Talley TT, Hansen SB, Taylor P, Marchot P (2005) Crystal structure of a Cbtx-AChBP complex reveals essential interactions between snake -neurotoxins and nicotinic receptors. EMBO J 24: 1512–1522] and the binding mode are shown.

Gln105 Trp147 Ile106

Tyr188 Val 108

Cys191 Tyr195

Fig. 1 Left: two perspectives of the nicotinic binding site of AChBP bound to the agonist epibatidine (PDB code 2BYQ). The pentameric receptor subunits are colored by chain, while ligand is shown in black. Right: detailed binding mode of the epibatidine on AChBP. The C trace of the receptor is displayed as a ribbon. The side chains of some relevant residues are shown as thick sticks, with C atoms coloured according to their subunit. Epibatidine C atoms are coloured in magenta Table 1. Docking scores, order of cluster and population of each type of complex found in the docking studies performed with Autodock into the nAChR binding site.

Order of Population of Score Store (first Compound cluster cluster (kcal/mol) ranked cluster) Epibatidine 1 80 -8.93 -8.93 1 5 40 -9.59 -10.04 2 1 46 -9.91 -9.91 3 1 12 -10.49 -10.49 4 5 1 -9.24 -10.20 5 1 97 -10.03 -10.03 6 - - - -8.88

Table 2. Docking scores, order of cluster and population of each type of complex found in the docking studies performed with FlexX into the nAChR binding site.

Order of Score Store (first Compound cluster (kJ/mol) ranked cluster) Epibatidine 1 -12.26 -12.26 1 5 -10.91 -12.13 2 1 -13.93 -13.93 3 8 -13.21 -15.35 4 - - -13.86 5 1 -13.29 -13.29 6 - - -12.59