Table 1. List of simulations.

Simulation namea,b	NMR restraints initially applied	Length (ns)
Fox-1 structure
2err_14_1	No	1000
2err_14_2	No	1000
2err_14_rst1	Yes	1000
2err_14_rst2	Yes	1000
2err_14_rst3	Yes	1000
2err_12_1	No	1000
2err_12_2	No	1000
2err_12_rst1	Yes	1000
2err_12_rst2	Yes	1000
2err_12_rst3	Yes	1000
2err_12_rst4	Yes	1000
2err_99_1	No	1000
2err_99_2	No	1000
2err_99_rst1	Yes	1000
2err_99_rst2	Yes	1000
2err_99_rst3	Yes	1000
2err_99_rst4	Yes	1000
SRSF1 structure
2m8d_14_1	No	1000
2m8d_14_2	No	1000
2m8d_14_rst1	Yes	1000
2m8d_14_rst2	Yes	1000
2m8d_14_rst3	Yes	1000
2m8d_14_rst4	Yes	1000
2m8d_12_1	No	1000
2m8d_12_2	No	1000
2m8d_12_rst1	Yes	1000
2m8d_12_rst2	Yes	1000
2m8d_12_rst3	Yes	1000
2m8d_12_rst4	Yes	1000
2m8d_12_rst5	Yes	1000
2m8d_99_1	No	700
2m8d_99_2	No	600
2m8d_99_rst1	Yes	1000
2m8d_99_rst2	Yes	1000
2m8d_99_rst3	Yes	1000
2m8d_99_rst4	Yes	1000
2m8d_99_rst5	Yes	1000
2m8d_14_short1c	Yes	1000
2m8d_14_short2c	Yes	1000
2m8d_12_short1c	Yes	1000
2m8d_12_short2c	Yes	1000
2m8d_99_short1c	Yes	2000
2m8d_99_short2c	Yes	1000
2m8d_14_R142Ad	No	1000
2m8d_12_R142Ad	No	4000
2m8d_12_R142A_2d	No	2000
2m8d_12_R142A_TI_1e	No	54 × 50
2m8d_12_R142A_TI_2e	No	54 × 200

^aAfter 120 ns of the simulation (unrestrained part, see Materials and Methods section), all of the initially restrained trajectories (marked as ‘_rst’) are fully independent simulation runs. However, up to 120 ns, some of them share a common restrained part of the trajectory. Full explanation is in the Supplementary Scheme S1.

^bThe ‘14’, ‘12’ and ‘99’ numerals in the simulation name indicate ff14SB, ff12SB and ff99SB protein force field versions, respectively. For the RNA, the ff99bsc0χ_OL3 force field was used in all simulations.

^cThe nucleotides 1–3 and amino-acids 106–114 were removed.

^dThe R142A mutation was introduced into the system by molecular modeling, with the final structure of the 2m8d_12_rst1 simulation used as the starting configuration.

^eBoth TI calculations consist of 54 independent simulations, each lasting either 50 (first simulation run) or 200 ns (second simulation run).