Table S1.

ALS-linked mutations stabilize SOD1 trimer

Original AA	Residue	Mutation	ΔΔGT	ΔΔGD	ΔΔGM
A	4	S	−9.51	5.728	−2.256
A	4	T	−12.996	9.072	−2.741
A	4	V	−4.844	8.659	0.62
V	7	E	−3.711	12.873	−4.104
L	8	Q	−1.052	12.078	1.658
L	8	V	−6.481	1.131	4.981
G	10	R	15.741	20	2.724
G	10	V	16.084	20	−2.917
G	12	R	−2.968	20	2.05
G	16	S	−5.171	19.269	6.765
N	19	S	−7.77	2.324	−2.961
E	21	K	−10.52	4.360	1.798
Q	22	L	−11.609	4.624	−6.264
G	37	R	−7.104	7.437	22.474
L	38	V	−2.494	−0.416	6.446
G	41	D	2.055	0.098	−3.873
G	41	S	−1.33	1.254	−1.104
H	46	R	−1.715	7.855	−1.624
H	48	Q	−5.294	6.819	0.665
H	48	R	−2.546	5.670	−5.052
N	65	S	3.241	1.199	−0.813
D	76	V	−6.563	12.791	2.922
D	76	Y	−6.816	2.921	−1.19
G	93	A	−3.804	12.803	0.707
G	93	D	22.897	20	−0.728
G	93	R	33.12	20	−0.087
G	93	S	2.8	20	9.944
G	93	V	20.699	14.997	15.008
A	95	T	−15.237	16.537	−0.281
D	101	G	−0.759	4.967	−1.86
D	101	H	0.31	9.361	0.142
D	101	N	−8.335	−1.371	−1.119
D	101	Y	0.921	14.853	−1.064
I	104	F	19.486	20	6.935
S	105	L	−14.356	−7.769	−6.383
L	106	F	13.187	20	2.706
L	106	V	7.353	4.349	−2.924
I	112	M	−3.703	−7.888	−1.988
I	112	T	−4.586	6.172	2.826
G	114	A	−10.812	11.700	−1.375
R	115	G	−3.484	−0.425	0.439
V	118	L	2.858	8.345	−4.0
D	124	G	−6.602	7.756	−4.152
D	125	H	−6.848	5.791	−3.271
L	127	R	−2.293	20	24.563
S	134	N	−8.502	3.170	6.118
G	141	E	21.177	7.283	1.218
A	145	T	−8.669	5.199	4.399
G	147	R	24.122	20	20.585
V	148	G	1.548	13.447	−5.315
V	148	I	−11.136	−2.324	2.884

Predicted ΔΔG (in kilocalories per mole) for known ALS disease mutations on structures of the SOD1 trimer, dimer, and monomer. Dimer and monomer structures are from Protein Data Bank ID code 1SPD; trimer structure, as in the main text, is model 1 described in Dataset S1. We note that our identified mutations for stabilizing or destabilizing the SOD1 trimer are not known disease mutants, likely because we specially selected them to affect only the trimeric form of SOD1 and not the native monomer or dimer species, artificially limiting our choices. Our purpose in choosing such mutations was for clean, unambiguous results verifying the identity of residues in the trimer interfaces, whereas the disease is most likely caused by mutations that affect the stability of all forms of SOD1, including the native forms for which we deselect here. AA, amino acid; ΔΔG_D, change in free energy upon mutation for the structure of SOD1 native dimer; ΔΔG_M, change in free energy upon mutation for the structure of SOD1 native monomer; ΔΔG_T, change in free energy upon mutation for the structure of SOD1 trimer.