Table 2. Summary of NOE distances violation and energy penalties for the DDD sequence using the NMR data obtained in-house (see ‘Materials and Methods’ section)^a.

Structure	N° of violations	Energy penaltyb (kcal/mol)	Average violation (Å)	Largest violation (Å)
BSC1-NOE	8	20.4	0.35	0.46
BSC0-NOE	9	22.7	0.35	0.43
BSC0OL15-NOE	14	35.0	0.35	0.47
Standard NMR	5	11.3	0.33	0.40
1NAJc	35	159.2	0.47	0.63
1GIPc	50	265.4	0.51	1.06
X-RAYc	46	332.1	0.60	1.58

^aTaking T as 298.15 K, the kT constant has a value of 0.5924812 kcal mol⁻¹. We considered an experimental restraint violated when its average penalty energy was above 3·kT. Given the force constant used to apply the distance restraints (k_res = 20 kcal/Ų), 3·kT is equivalent to set a tolerance of ±0.3 Å on the experimental range to consider that a specific distance has been violated.

^bFor each distance the energy penalty (E_pen) was computed as: E_pen = k_res(dist_calc-dist_obs)². Note that we simply reported the sum of each individual E_pen.

^cA single-point calculation in vacuo was performed on the average experimental structure applying our NMR restraints.