Table 1: Evaluation of the optimized R₂-dynamic and ${\text{S}}^2$-dynamic ensembles and original ensembles for ENSEMBLE, RANDOM, and MIXED pools with 8 experimental data types.

We report both the X-EISD score, and the root mean square deviations (RMSD) with experiments. The results shown here are optimized with all experimental data types. The experimental and back calculations errors for CSs (${\text{σ}}_{\text{exp}}=0.03-0.3$ ppm; ${\text{σ}}_{\text{q}}=0.3-0.5$ ppm (hydrogen), 1.2–1.4 ppm (carbon)); JCs (${\text{σ}}_{\exp }=0.5$; ${\text{σ}}_{\text{q},\text{A}}=0.14$, ${\text{σ}}_{\text{q},\text{B}}=0.03$,${\text{σ}}_{\text{q},\text{C}}=0.08$); RDCs (${\text{σ}}_{\text{exp}}=1.0$; ${\text{σ}}_{\text{q}}=0.9$); NOEs (${\text{σ}}_{\text{exp}}=4.0-5.0\text{Å}$; ${\text{σ}}_{\text{q}}=0.0001$); PREs (${\text{σ}}_{\exp }=1.25-3.625\text{Å}$; ${\text{σ}}_{\text{q}}=0.0001$); smFRET <E> (${\text{σ}}_{\exp }=0.02$; ${\text{σ}}_{\text{q}}=0.007$); $R_h$ (${\text{σ}}_{\exp }=0.3$; ${\text{σ}}_q=0.8$); SAXS (${\text{σ}}_{\exp }=0.0008-0.002$, ${\text{σ}}_{\text{q}}=0.0006$).

Experimental data type	$\text{R}2$-Dynamic Pool		${\text{S}}^2$-Dynamic Pool		Original Pool
	X-EISD Score	RMSD	X-EISD Score	RMSD	X-EISD Score	RMSD
ENSEMBLE
CS (ppm)	117.5 (0.4)	0.3 (0.005)	117.9 (0.3)	0.34 (0.004)	110.1 (0.4)	0.51 (0)
JC (Hz)	43.68 (0.41)	0.16 (0.008)	41.2 (0.4)	0.21 (0.007)	43.3 (0.5)	0.18 (0.01)
RDC (Hz)	−47.8 (0.003)	0.04 (0.005)	−50.1 (0.2)	0.54 (0.02)	−50.4 (0.2)	0.56 (0.03)
NOE ($\text{Å}$)	534.8 (0.4)	2.6 (0.03)	533.7 (0.4)	2.7 (0.03)	532.2 (0.5)	2.8 (0.03)
PRE ($\text{Å}$)	460.4 (2.1)	0.86 (0.06)	443.6 (1.0)	1.42 (0.03)	453.9 (1.7)	1.02 (0.11)
smFRET <E>	6.91 (0.05)	0.006 (0.003)	6.95 (0.03)	0.004 (0.002)	7.0 (0)	0 (0)
Rh ($\text{Å}$)	−0.42 (0)	0	−0.57 (0.02)	0.47 (0.03)	−0.8 (0)	0.71 (0.04)
SAXS (Intensity)	458.3 (0.2)	0.001 (0)	458.0 (0.2)	0.001 (0)	457.9 (0.2)	0.001 (0)
RANDOM
CS (ppm)	118.3 (0.03)	0.33 (0.002)	109.59 (0.66)	0.47 (0.006)	103.6 (0.7)	0.55 (0.01)
JC (Hz)	−47.6 (1.7)	0.78 (0.006)	−34.39 (3.03)	0.73 (0.01)	−25.7 (2.4)	0.7 (0.01)
RDC (Hz)	−48.4 (0.02)	0.2 (0.007)	52.2 (0.02)	0.2 (0.007)	−55.4 (0.6)	0.98 (0.04)
NOE ($\text{Å}$)	506.0 (1.2)	4.3 (0.05)	526.03 (1.77)	3.20 (0.10)	528.5 (1.5)	3.06 (0.10)
PRE ($\text{Å}$)	261.1 (4.0)	3.4 (0.03)	429.53 (5.61)	1.69 (0.11)	450.0 (4.4)	1.24 (0.12)
smFRET <E>	3.9 (0.7)	0.05 (0.006)	6.84 (0.15)	0.009 (0.006)	6.9 (0.1)	0.01 (0)
Rh ($\text{Å}$)	−0.42 (0.1)	0	−0.47 (0.1)	0	−0.4 (0)	0.14 (0.10)
SAXS (Intensity)	452.4 (0.9)	0.003 (0)	455.03 (0.81)	0.002 (0)	456.3 (0.4)	0.002 (0)
MIXED
CS (ppm)	118.6 (0.45)	0.34 (0.006)	119.6 (0.3)	0.32 (0.005)	115.5 (0.5)	0.49 (0.01)
JC (Hz)	41.2 (0.60)	0.21 (0.01)	39.59 (0.66)	0.23 (0.01)	41.4 (0.7)	0.21 (0.01)
RDC (Hz)	−51.17 (0.35)	0.64 (0.03)	−51.16 (0.3)	0.62 (0.03)	−50.7 (0.3)	0.60 (0.03)
NOE ($\text{Å}$)	535.8 (0.66)	2.6 (0.04)	533.02 (0.53)	2.81 (0.04)	539.4 (0.7)	2.28 (0.07)
PRE ($\text{Å}$)	459.7 (2.3)	0.89 (0.06)	446.4 (1.8)	1.33 (0.03)	458.4 (4.3)	0.92 (0.11)
smFRET <E>	6.9 (0.08)	0.007 (0.004)	6.9 (0.05)	0.005 (0.004)	6.9 (0)	0.01 (0)
Rh ($\text{Å}$)	0.54 (0.05)	0.41 (0.09)	−0.46 (0.02)	0.21 (0.08)	−0.7 (0)	0.69 (0.05)
SAXS (Intensity)	457.5 (0.33)	0.002 (0)	457.9 (0.2)	0.001 (0)	458.0 (0.2)	0.001 (0)