mm~qmmm

Results calculated with edgembar version 3.2 on Thu Aug 1 11:29:39 2024 using the command:

edgembar_omp --no-auto xml/mm~qmmm.xml

There are a total of 2 errors and 8 warnings. The most severe errors (without repeats) are listed below.

Errors reported because the simulations did not equilibrate:
ΔG(tgt,STA,#t03,λ:0.20000000)

Warnings reported because most of the simulation should be discarded:
ΔG(tgt,STA,#t01,λ:1.00000000)
ΔG(tgt,STA,#t03,λ:0.40000000)
ΔG(tgt,STA,#t03,λ:1.00000000)
ΔG(tgt,STA,#t04,λ:1.00000000)
ΔG(ref,STA,#t01,λ:0.20000000)
ΔG(ref,STA,#t02,λ:0.00000000)
ΔG(ref,STA,#t03,λ:0.20000000)
ΔG(ref,STA,#t04,λ:0.00000000)

⟨ΔΔG⟩ Shifted Edge Objective Function (kcal/mol)

The objective function polynomial fit is of the form:

F(x) = c0 + c2*(x-x0)^2 + c3*(x-x0)^3

where x0=9.1635899826e+00 c0=1.5137783344e+00 c2=1.3072288558e-02 c3=-2.7250368701e-06. The plot excludes the c0 term.

A cubic fit produces a Pearson correlation of 1.00000.

A quadratic fit produces a Pearson correlation of 1.00000.

The relative free energy ⟨ΔΔG⟩ is the difference in complexed and solvated environments:
⟨ΔΔG⟩ = ⟨ΔG(tgt,STA)⟩ - ⟨ΔG(ref,STA)⟩
Click here to see ⟨ΔG(tgt,STA)⟩
Click here to see ⟨ΔG(ref,STA)⟩

Decomposition of ⟨ΔΔG⟩ into environmental ΔG values

Sampling	⟨ΔΔG⟩	⟨ΔG(tgt)⟩	⟨ΔG(ref)⟩	⟨f_eq⟩	⟨g_prod⟩
Prod.	9.164 ± 0.217	-143776.395 ± 0.216	-143785.559 ± 0.024	0.39	3

Comparison of ⟨ΔΔG⟩ MBAR and TI results

Method	ΔG	ΔG-MBAR	T
Linear Interp.	9.163 ± 0.234	-0.001 ± 0.319	0.003
Natural Cubic	9.166 ± 0.236	0.003 ± 0.321	0.008
Clamped Cubic	9.163 ± 0.234	-0.001 ± 0.319	0.003
MBAR	9.164 ± 0.217

The free energy ⟨ΔG(tgt,STA)⟩ is the average:
⟨ΔG(tgt,STA)⟩ = (1/4) [ ΔG(tgt,STA,#t01) + ΔG(tgt,STA,#t02) + ΔG(tgt,STA,#t03) + ΔG(tgt,STA,#t04) ]
Click here to see ΔG(tgt,STA,#t01)
Click here to see ΔG(tgt,STA,#t02)
Click here to see ΔG(tgt,STA,#t03)
Click here to see ΔG(tgt,STA,#t04)
The free energy ⟨ΔG(tgt,STA)⟩ was used in the calculation of the following quantities:
Click here to see ⟨ΔΔG⟩

Decomposition of ⟨ΔG(tgt,STA)⟩ into trials

Sampling	⟨ΔG(tgt,STA)⟩	ΔG(tgt,STA,#t01)	ΔG(tgt,STA,#t02)	ΔG(tgt,STA,#t03)	ΔG(tgt,STA,#t04)
Prod.	-143776.395 ± 0.216	-143775.804 ± 0.114	-143776.535 ± 0.097	-143776.792 ± 0.106	-143776.449 ± 0.087

Comparison of ⟨ΔG(tgt,STA)⟩ MBAR and TI results

Method	ΔG	ΔG-MBAR	T
Linear Interp.	-143776.250 ± 0.231	0.145 ± 0.316	0.458
Natural Cubic	-143776.332 ± 0.234	0.063 ± 0.319	0.199
Clamped Cubic	-143776.250 ± 0.231	0.145 ± 0.316	0.458
MBAR	-143776.395 ± 0.216

The free energy ⟨ΔG(ref,STA)⟩ is the average:
⟨ΔG(ref,STA)⟩ = (1/4) [ ΔG(ref,STA,#t01) + ΔG(ref,STA,#t02) + ΔG(ref,STA,#t03) + ΔG(ref,STA,#t04) ]
Click here to see ΔG(ref,STA,#t01)
Click here to see ΔG(ref,STA,#t02)
Click here to see ΔG(ref,STA,#t03)
Click here to see ΔG(ref,STA,#t04)
The free energy ⟨ΔG(ref,STA)⟩ was used in the calculation of the following quantities:
Click here to see ⟨ΔΔG⟩

Decomposition of ⟨ΔG(ref,STA)⟩ into trials

Sampling	⟨ΔG(ref,STA)⟩	ΔG(ref,STA,#t01)	ΔG(ref,STA,#t02)	ΔG(ref,STA,#t03)	ΔG(ref,STA,#t04)
Prod.	-143785.559 ± 0.024	-143785.525 ± 0.042	-143785.590 ± 0.037	-143785.572 ± 0.031	-143785.547 ± 0.047

Comparison of ⟨ΔG(ref,STA)⟩ MBAR and TI results

Method	ΔG	ΔG-MBAR	T
Linear Interp.	-143785.413 ± 0.037	0.146 ± 0.044	3.277
Natural Cubic	-143785.498 ± 0.032	0.061 ± 0.040	1.504
Clamped Cubic	-143785.413 ± 0.037	0.146 ± 0.044	3.277
MBAR	-143785.559 ± 0.024

The free energy ΔG(tgt,STA,#t01) was used in the calculation of the following quantities:
Click here to see ⟨ΔΔG⟩
Click here to see ⟨ΔG(tgt,STA)⟩

ΔG(tgt,STA,#t01)

Traj	ΔG	Prod. Region					All Data		S	RE
	MBAR	f_eq	N_eq	g_prod	g_ana	N_ana	g	N	Fwd	Fwd	Rev
0.00000000	0.000 ± 0.000	0.55	275	3	3	500	3	500	0.50	0.88
0.20000000	-28753.805 ± 0.040	0.55	275	6	10	500	10	500	0.53	0.89	0.86
0.40000000	-57508.531 ± 0.070	0.60	300	13	23	500	23	500	0.87	0.93	0.92
0.60000000	-86263.846 ± 0.094	0.60	300	3	10	500	10	500	0.92	0.93	0.94
0.80000000	-115019.615 ± 0.108	0.50	250	8	10	500	10	500	0.76	0.94	0.93
1.00000000	-143775.804 ± 0.114	0.65	325	3	7	500	7	500			0.93

Comparison of ΔG(tgt,STA,#t01) MBAR and TI results

Method	ΔG	ΔG-MBAR	T
Linear Interp.	-143775.660 ± 0.206	0.144 ± 0.235	0.613
Natural Cubic	-143775.717 ± 0.213	0.088 ± 0.242	0.363
Clamped Cubic	-143775.660 ± 0.206	0.144 ± 0.235	0.613
MBAR	-143775.804 ± 0.114

ΔG(tgt,STA,#t01) DV/DL (kcal/mol)

The free energy ΔG(tgt,STA,#t02) was used in the calculation of the following quantities:
Click here to see ⟨ΔΔG⟩
Click here to see ⟨ΔG(tgt,STA)⟩

ΔG(tgt,STA,#t02)

Traj	ΔG	Prod. Region					All Data		S	RE
	MBAR	f_eq	N_eq	g_prod	g_ana	N_ana	g	N	Fwd	Fwd	Rev
0.00000000	0.000 ± 0.000	0.20	100	5	5	500	5	500	0.55	0.89
0.20000000	-28754.002 ± 0.027	0.40	200	6	10	500	10	500	0.77	0.91	0.85
0.40000000	-57508.828 ± 0.043	0.25	125	3	16	500	16	500	0.71	0.92	0.88
0.60000000	-86264.260 ± 0.061	0.30	150	6	6	500	6	500	0.67	0.95	0.94
0.80000000	-115020.190 ± 0.080	0.60	300	6	6	500	6	500	0.91	0.95	0.94
1.00000000	-143776.535 ± 0.097	0.20	100	4	7	500	7	500			0.95

Comparison of ΔG(tgt,STA,#t02) MBAR and TI results

Method	ΔG	ΔG-MBAR	T
Linear Interp.	-143776.421 ± 0.221	0.113 ± 0.242	0.469
Natural Cubic	-143776.500 ± 0.218	0.034 ± 0.239	0.144
Clamped Cubic	-143776.421 ± 0.221	0.113 ± 0.242	0.469
MBAR	-143776.535 ± 0.097

ΔG(tgt,STA,#t02) DV/DL (kcal/mol)

The free energy ΔG(tgt,STA,#t03) was used in the calculation of the following quantities:
Click here to see ⟨ΔΔG⟩
Click here to see ⟨ΔG(tgt,STA)⟩

ΔG(tgt,STA,#t03)

Traj	ΔG	Prod. Region					All Data		S	RE		Conv?
	MBAR	f_eq	N_eq	g_prod	g_ana	N_ana	g	N	Fwd	Fwd	Rev
0.00000000	0.000 ± 0.000	0.05	25	8	10	500	10	500	0.63	0.85
0.20000000	-28754.126 ± 0.045	0.75	375	2	7	500	7	500	0.62	0.90	0.87	No
0.40000000	-57509.049 ± 0.072	0.70	350	10	9	500	9	500	0.78	0.92	0.89
0.60000000	-86264.528 ± 0.088	0.35	175	4	11	500	11	500	0.79	0.94	0.93
0.80000000	-115020.456 ± 0.098	0.25	125	13	13	500	13	500	0.90	0.95	0.93
1.00000000	-143776.792 ± 0.106	0.70	350	5	10	500	10	500			0.94

Comparison of ΔG(tgt,STA,#t03) MBAR and TI results

Method	ΔG	ΔG-MBAR	T
Linear Interp.	-143776.596 ± 0.230	0.196 ± 0.254	0.773
Natural Cubic	-143776.629 ± 0.235	0.163 ± 0.258	0.633
Clamped Cubic	-143776.596 ± 0.230	0.196 ± 0.254	0.773
MBAR	-143776.792 ± 0.106

ΔG(tgt,STA,#t03) DV/DL (kcal/mol)

The free energy ΔG(tgt,STA,#t04) was used in the calculation of the following quantities:
Click here to see ⟨ΔΔG⟩
Click here to see ⟨ΔG(tgt,STA)⟩

ΔG(tgt,STA,#t04)

Traj	ΔG	Prod. Region					All Data		S	RE
	MBAR	f_eq	N_eq	g_prod	g_ana	N_ana	g	N	Fwd	Fwd	Rev
0.00000000	0.000 ± 0.000	0.50	250	5	7	500	7	500	0.35	0.86
0.20000000	-28753.947 ± 0.047	0.60	300	6	6	500	6	500	0.77	0.90	0.88
0.40000000	-57508.783 ± 0.068	0.50	250	4	14	500	14	500	0.91	0.93	0.93
0.60000000	-86264.173 ± 0.080	0.55	275	5	17	500	17	500	0.47	0.94	0.91
0.80000000	-115020.079 ± 0.083	0.50	250	7	8	500	8	500	0.92	0.95	0.95
1.00000000	-143776.449 ± 0.087	0.70	350	1	9	500	9	500			0.95

Comparison of ΔG(tgt,STA,#t04) MBAR and TI results

Method	ΔG	ΔG-MBAR	T
Linear Interp.	-143776.324 ± 0.191	0.125 ± 0.210	0.595
Natural Cubic	-143776.481 ± 0.196	-0.032 ± 0.214	0.148
Clamped Cubic	-143776.324 ± 0.191	0.125 ± 0.210	0.595
MBAR	-143776.449 ± 0.087

ΔG(tgt,STA,#t04) DV/DL (kcal/mol)

The free energy ΔG(ref,STA,#t01) was used in the calculation of the following quantities:
Click here to see ⟨ΔΔG⟩
Click here to see ⟨ΔG(ref,STA)⟩

ΔG(ref,STA,#t01)

Traj	ΔG	Prod. Region					All Data		S	RE
	MBAR	f_eq	N_eq	g_prod	g_ana	N_ana	g	N	Fwd	Fwd	Rev
0.00000000	0.000 ± 0.000	0.30	150	2	7	500	7	500	0.36	0.90
0.20000000	-28756.431 ± 0.024	0.70	350	1	1	500	1	500	0.82	0.96	0.93
0.40000000	-57513.386 ± 0.031	0.25	125	1	1	500	1	500	0.87	0.97	0.96
0.60000000	-86270.587 ± 0.036	0.40	200	1	1	500	1	500	0.94	0.98	0.96
0.80000000	-115027.972 ± 0.040	0.00	0	1	1	500	1	500	0.91	0.97	0.97
1.00000000	-143785.525 ± 0.042	0.45	225	1	1	500	1	500			0.98

Comparison of ΔG(ref,STA,#t01) MBAR and TI results

Method	ΔG	ΔG-MBAR	T
Linear Interp.	-143785.404 ± 0.056	0.121 ± 0.070	1.717
Natural Cubic	-143785.495 ± 0.051	0.030 ± 0.066	0.459
Clamped Cubic	-143785.404 ± 0.056	0.121 ± 0.070	1.717
MBAR	-143785.525 ± 0.042

ΔG(ref,STA,#t01) DV/DL (kcal/mol)

The free energy ΔG(ref,STA,#t02) was used in the calculation of the following quantities:
Click here to see ⟨ΔΔG⟩
Click here to see ⟨ΔG(ref,STA)⟩

ΔG(ref,STA,#t02)

Traj	ΔG	Prod. Region					All Data		S	RE
	MBAR	f_eq	N_eq	g_prod	g_ana	N_ana	g	N	Fwd	Fwd	Rev
0.00000000	0.000 ± 0.000	0.65	325	1	3	500	3	500	0.48	0.92
0.20000000	-28756.504 ± 0.020	0.50	250	1	1	500	1	500	0.69	0.96	0.89
0.40000000	-57513.468 ± 0.028	0.25	125	1	1	500	1	500	0.88	0.97	0.97
0.60000000	-86270.664 ± 0.032	0.00	0	1	1	500	1	500	0.91	0.98	0.97
0.80000000	-115028.042 ± 0.035	0.30	150	1	1	500	1	500	0.85	0.98	0.98
1.00000000	-143785.590 ± 0.037	0.25	125	1	1	500	1	500			0.97

Comparison of ΔG(ref,STA,#t02) MBAR and TI results

Method	ΔG	ΔG-MBAR	T
Linear Interp.	-143785.465 ± 0.052	0.125 ± 0.064	1.958
Natural Cubic	-143785.527 ± 0.048	0.063 ± 0.060	1.042
Clamped Cubic	-143785.465 ± 0.052	0.125 ± 0.064	1.958
MBAR	-143785.590 ± 0.037

ΔG(ref,STA,#t02) DV/DL (kcal/mol)

The free energy ΔG(ref,STA,#t03) was used in the calculation of the following quantities:
Click here to see ⟨ΔΔG⟩
Click here to see ⟨ΔG(ref,STA)⟩

ΔG(ref,STA,#t03)

Traj	ΔG	Prod. Region					All Data		S	RE
	MBAR	f_eq	N_eq	g_prod	g_ana	N_ana	g	N	Fwd	Fwd	Rev
0.00000000	0.000 ± 0.000	0.50	250	3	2	500	2	500	0.34	0.90
0.20000000	-28756.461 ± 0.022	0.70	350	1	1	500	1	500	0.87	0.97	0.93
0.40000000	-57513.422 ± 0.025	0.00	0	1	1	500	1	500	0.92	0.97	0.96
0.60000000	-86270.620 ± 0.027	0.00	0	1	1	500	1	500	0.85	0.97	0.96
0.80000000	-115028.007 ± 0.028	0.05	25	1	1	500	1	500	0.92	0.98	0.98
1.00000000	-143785.572 ± 0.031	0.00	0	1	1	500	1	500			0.98

Comparison of ΔG(ref,STA,#t03) MBAR and TI results

Method	ΔG	ΔG-MBAR	T
Linear Interp.	-143785.433 ± 0.050	0.140 ± 0.059	2.375
Natural Cubic	-143785.526 ± 0.046	0.047 ± 0.055	0.840
Clamped Cubic	-143785.433 ± 0.050	0.140 ± 0.059	2.375
MBAR	-143785.572 ± 0.031

ΔG(ref,STA,#t03) DV/DL (kcal/mol)

The free energy ΔG(ref,STA,#t04) was used in the calculation of the following quantities:
Click here to see ⟨ΔΔG⟩
Click here to see ⟨ΔG(ref,STA)⟩

ΔG(ref,STA,#t04)

Traj	ΔG	Prod. Region					All Data		S	RE
	MBAR	f_eq	N_eq	g_prod	g_ana	N_ana	g	N	Fwd	Fwd	Rev
0.00000000	0.000 ± 0.000	0.70	350	3	4	500	4	500	0.35	0.90
0.20000000	-28756.437 ± 0.032	0.20	100	3	4	500	4	500	0.75	0.96	0.90
0.40000000	-57513.412 ± 0.041	0.25	125	1	1	500	1	500	0.81	0.98	0.96
0.60000000	-86270.619 ± 0.044	0.30	150	1	1	500	1	500	0.92	0.98	0.98
0.80000000	-115028.003 ± 0.046	0.35	175	1	1	500	1	500	0.90	0.98	0.97
1.00000000	-143785.547 ± 0.047	0.25	125	1	1	500	1	500			0.98

Comparison of ΔG(ref,STA,#t04) MBAR and TI results

Method	ΔG	ΔG-MBAR	T
Linear Interp.	-143785.350 ± 0.064	0.197 ± 0.080	2.470
Natural Cubic	-143785.444 ± 0.059	0.103 ± 0.076	1.361
Clamped Cubic	-143785.350 ± 0.064	0.197 ± 0.080	2.470
MBAR	-143785.547 ± 0.047

ΔG(ref,STA,#t04) DV/DL (kcal/mol)

ΔUfwd(tgt,STA,#t03,λ:0.20000000) mm~qmmm Fwd & Rev Analysis (kcal/mol)	ΔUfwd(tgt,STA,#t03,λ:0.20000000) mm~qmmm First- & Last-Half Analysis (kcal/mol)

ΔUrev(tgt,STA,#t03,λ:0.20000000) mm~qmmm Fwd & Rev Analysis (kcal/mol)	ΔUrev(tgt,STA,#t03,λ:0.20000000) mm~qmmm First- & Last-Half Analysis (kcal/mol)

Click here to see ΔG(tgt,STA,#t03)

ΔU(tgt,STA,#t03,λ:0.20000000)

f0	fN	ΔUfwd						ΔUrev
		Δ	T		KS	N		Δ	T		KS	N
		Production region elongation						Production region elongation
0.45	0.50	0.22 ± 0.39	0.57 > 0.32	or	0.73 > 0.32	31 ≥ 28	Y	0.22 ± 0.39	0.57 > 0.32	or	0.73 > 0.32	31 ≥ 28	Y
0.40	0.50	0.54 ± 0.32	0.10 > 0.32	or	0.00 > 0.32	50 ≥ 31	N	0.54 ± 0.32	0.10 > 0.32	or	0.00 > 0.32	50 ≥ 31	N
0.35	0.50	0.91 ± 0.38	0.02 > 0.32	or	0.00 > 0.32	47 ≥ 31	N	0.91 ± 0.38	0.02 > 0.32	or	0.00 > 0.32	47 ≥ 31	N
0.30	0.50	0.87 ± 0.32	0.01 > 0.32	or	0.00 > 0.32	30 ≥ 31	N	0.87 ± 0.32	0.01 > 0.32	or	0.00 > 0.32	30 ≥ 31	N
0.25	0.50	0.80 ± 0.28	0.01 > 0.32	or	0.00 > 0.32	35 ≥ 31	N	0.80 ± 0.28	0.01 > 0.32	or	0.00 > 0.32	35 ≥ 31	N
0.20	0.50	0.68 ± 0.30	0.03 > 0.32	and	0.00 > 0.32	50 ≥ 31	N	0.68 ± 0.30	0.03 > 0.32	and	0.00 > 0.32	50 ≥ 31	N
		Extended region: 0.45 to 1.00						Extended region: 0.45 to 1.00
0.45	1.00	0.39 ± 0.27	0.15 > 0.32			31	N	0.39 ± 0.27	0.15 > 0.32			31	N
0.50	1.00	0.59 ± 0.33	0.08 > 0.32			28	N	0.59 ± 0.33	0.08 > 0.32			28	N
0.55	1.00	0.74 ± 0.26	0.01 > 0.32			25	N	0.74 ± 0.26	0.01 > 0.32			25	N
0.60	1.00	0.82 ± 0.24	0.00 > 0.32			29	N	0.82 ± 0.24	0.00 > 0.32			29	N
0.65	1.00	0.87 ± 0.31	0.01 > 0.32			30	N	0.87 ± 0.31	0.01 > 0.32			30	N
0.70	1.00	0.48 ± 0.28	0.09 > 0.32			50	N	0.48 ± 0.28	0.09 > 0.32			50	N
0.75	1.00	0.32 ± 0.27	0.23 > 0.32			63	N	0.32 ± 0.27	0.23 > 0.32			63	N
		Convergence not found. Compare last 0.25 with extended region						Convergence not found. Compare last 0.25 with extended region
		0.26 ± 0.25	0.30 > 0.32				N	0.26 ± 0.25	0.30 > 0.32				N