Table 2.
Ligand/receptor distances (Å) in the final MD structures
| Ligand | α3β4 | α4β2 | AChPB | |||
|---|---|---|---|---|---|---|
| Acetylcholine | ||||||
| N+ | αTrp146(ring) | 4.8 | αTrp146(ring) | 4.5 | +Tyr184(ring) | 4.8 |
| αTyr90(OH) | 4.3 | αTyr90(OH) | 4.7 | +Tyr191(ring) | 4.6 | |
| αTrp146(O) | 4.3 | αTrp146(O) | 4.2 | −Trp52(ring) | 4.6 | |
| 3H2O(O) | <5.0 | H2O(O) | 3.9 | +Tyr88(OH) | 4.3 | |
| C4 | αCys189(S) | 3.5 | — | — | — | — |
| C3 | αTrp146(ring) | 3.7 | αCys189(S) | 3.7 | +Trp142(ring) | 3.5 |
| C1 | βLeu118(Cδ) | 4.4 | βPhe116(ring) | 4.0 | — | — |
| O | H2O(O) | 2.8 | H2O(O) | 3.1 | — | — |
| Nicotine | ||||||
| N+ | αTyr194(ring) | 4.8 | αTrp146(ring) | 4.8 | −Trp52(ring) | 4.8 |
| αTyr90(OH) | 4.4 | αTyr90(OH) | 4.3 | — | — | |
| H2O(O) | 4.8 | αTrp146(O) | 4.2 | — | — | |
| — | — | 3H2O(O) | <5.0 | — | — | |
| Ring (I) | αTrp146(ring) | 3.6 | αTyr187(ring ⊥) | 3.4 | +Tyr88(ring ⊥) | 4.7 |
| αCys189(S) | 3.5 | — | — | +Trp142(ring) | 4.7 | |
| — | — | — | — | +Tyr184(ring ⊥) | 4.3 | |
| — | — | — | — | +Tyr191(ring) | 4.2 | |
| N | βLeu118(O) | 2.8 | — | — | +Tyr191(OH) | 3.2 |
| αTyr194(OH) | 3.2 | — | — | — | — | |
| Ring (II) | αTrp146(O) | 2.8 | βPhe116(ring) | 3.4 | +Cyx187(S) | 3.4 |
| βLeu118(Cδ) | 4.0 | αCys189(S) | 3.9 | −Met113(S) | 3.9 | |
| Cytisine | ||||||
| N+ | αTyr194(ring) | 3.8 | αTyr194(ring) | 3.4 | +Tyr88(OH) | 3.1 |
| αTyr90(OH) | 4.3 | αTyr90(OH) | 3.1 | +Ser141(O) | 3.6 | |
| αSer145(O) | 4.2 | αTrp146(O) | 3.1 | H2O(O) | 4.4 | |
| αTrp146(O) | 3.1 | H2O(O) | 4.7 | — | — | |
| Ring (I) | — | — | αTyr187(ring ⊥) | 4.0 | +Tyr88(ring ⊥) | 3.7 |
| — | — | — | — | +Tyr184(ring) | 4.2 | |
| — | — | — | — | +Tyr191(ring ⊥) | 4.2 | |
| Ring(I) | αTrp146(ring ⊥) | 3.7 | αTrp146(ring ⊥) | 3.8 | −Trp52(ring ⊥) | 3.8 |
| αCys190(S) | 4.0 | βLeu118(Cδ) | 3.4 | +Trp142(O) | 2.9 | |
| Ring(III) | βLeu118(Cδ) | 3.6 | βPhe116(ring) | 4.0 | +Cyx188(S) | 4.0 |
| βIle108(Cδ) | 3.3 | αCys190(S) | 3.5 | −Met113(S) | 3.9 | |
| O | H2O(O) | 3.2 | H2O(O) | 2.7 | +Trp142(ring) | 2.9 |
Note that the term (ring) after an amino-acid residue denotes either the interaction of the ligand N+ atom with the corresponding amino-acid ring (π-cation type of interaction) or the π–π planar interaction between the ring structure of nicotine (or cytisine) and the corresponding ring structure of the amino-acid residue on the receptor subunit. When one ring interacts orthogonally to the other, this reaction is indicated as ring ⊥.