Table 1. Ligand-channel energy (E, kcal/mol) and top contributions to it^a.

State	Ligand	K ions	E	K+	F103	T75	T74	I100
Open	Lidocaine	S1/S3	−23.4	0.37	−8.20	−4.15	−0.73	−2.52
		S2/S4	−15.1	2.42	−6.25	−1.61	−0.11	−2.12
	Tetracaine	S1/S3	−20.6b	0.74	−2.02	−1.36	−0.72	−1.09
		S2/S4	−13.4c	6.72	−9.17	−2.03	0.17	−0.75
Open- inactivated	Lidocaine	S1/S4	−17.5	0.58	−1.38	−6.64	−0.22	−2.17
	Tetracaine	S1/S4	−20.2	−0.38	−1.97	−2.99	−0.01	−2.57
Closed	Lidocaine	S2/S4	−19.4d	0.62	−2.3	−3.64	0.04	−3.79
	Tetracaine	S2/S4	−23.1e	3.51	−2.45	−3.54	−0.16	−2.86

^a Summed contributions from the sidechains of the four same-number residues and from both K ions. Contributions from backbones may be large, especially for Thr74 and Gly99, which may be tested by synthetic replacement with unnatural amino acids. ^bOther top contributors are Ser102 (−0.67), Leu36 (−0.86), Val97 (−0.61), Thr33 (−0.35), H₂O at site S₄ (−0.57), Val106 (−0.36) and Met96 (−0.50). ^cAnother top contributor is Thr107 (−0.68). ^dOther top contributors are Val106 (−0.93) and Thr107 (−0.37). ^eAnother top contributor is Thr107 (−3.53).