Table 1. Free Energies from One-step Perturbation for Both Reference States in the E105 Site^a.

P1′	mut at 105	RDR p_contr	RDR ΔΔGR>N	R2R p_contr	R2R ΔΔGR>N
Ile	Ala	89.7	–16.2	28.52	1.0
	Arg	0.52	110.2	16.15	–1.9
	Asn	26.99	–5.1	11.18	3.4
	Asp	30.38	–4.2	11.77	–4.6
	Cys	0.89	–10.5	2.84	–16.3
	Gly	2.11	–1.8	1.66	–6.9
	Gln	1.08	6.0	5.81	6.6
	Glu	17.99	–6.0	17.97	–1.2
	HisA	1.23	–24.3	6.03	–8.8
	HisB	0.84	–4.2	5.51	–7.0
	Ile	2.75	–14.7	3.00	–1.2
	Leu	4.97	–7.0	1.02	2.2
	Lys	0.25	–5.8	1.45	0.3
	Met	0.59	–20.7	5.18	2.4
	Phe	0.35	44.5	0.98	10.2
	Ser	65.53	3.7	16.27	–12.6
	Thr	26.89	–2.2	16.59	–2.6
	Trp	0.45	–79.2	0.30	67.2
	Tyr	0.56	–9.1	0.37	6.9
	Val	11.52	–1.2	8.14	–1.2
Pro	Ala	76.64	–9.9	25.70	–8.5
	Arg	0.60	162.3	18.84	–20.0
	Asn	8.47	–0.3	10.91	–11.8
	Asp	10.44	2.7	8.06	4.0
	Cys	0.78	4.0	6.13	0.6
	Gly	1.74	0.1	0.99	6.5
	Gln	0.45	4.3	6.03	14.6
	Glu	7.49	7.7	19.62	5.6
	HisA	5.28	15.0	17.22	–5.1
	HisB	16.48	–2.0	19.60	–8.4
	Ile	0.78	–7.2	3.13	3.0
	Leu	4.37	–1.4	0.67	16.2
	Lys	0.67	–69.4	8.21	–4.1
	Met	1.00	–16.1	7.58	–15.2
	Phe	0.39	36.0	8.43	–5.1
	Ser	31.17	2.8	10.00	8.0
	Thr	14.64	6.2	3.22	3.3
	Trp	0.47	–187.3	4.55	–21.7
	Tyr	0.45	485.5	1.91	12.0
	Val	6.51	2.3	13.28	–3.1

^aFree energies are reported for two P1′ amino acids, Ile and Pro. Next to the ΔΔG values (reported in kJ/mol), the percentage of contributing frames are reported as an average over both bound and unbound states. HisA: N^δ1-H tautomer; HisB: N^ϵ2–H tautomer.