TABLE 3.

Computed interaction energies of the indole side chain of W101 and of the ligand 77-LH-28-1 calculated using a structural model of the M₁ mAChR

A homology model of the M₁ mAChR was constructed on the structure of the β₂-adrenergic receptor and optimized (see Materials and Methods). Values are the sum of the calculated interaction energies between the indicated moieties, given as kilocalories per mole. Interaction energies for the indole side chain of Trp101 with the side chains of Tyr82 and Leu102 were calculated by energy deconvolution using a trans conformation (ϰ₁ = 167.7°) of the Trp101 side chain. After rotation of the side chain of Trp101 to give ϰ₁ = −60° (gauche⁺ conformation), 77-LH-28-1 was docked into the resulting binding pocket, and the resulting structure was subjected to final energy minimisation resulting in a ϰ₁ angle of −66° for Trp101. The interaction energies of the atoms of 77-LH-28-1 with Tyr82 and Leu102 were then calculated by energy deconvolution (see Materials and Methods).

Residue	Trp101 Indole Ring			77-LH-28-1
	Electronic	Steric	Total	Electronic	Steric	Total
			kcal/mol
Tyr 82	0.064	−2.246	−2.181	−0.131	−5.839	−5.969
Leu 102	−0.022	−2.827	−2.849	−0.073	−2.632	−2.706