Table 1.

Characterization of single-domain mutant proteins. Note that our spectrin domains have extensions at either end ³⁸. Residue 1 of the R16 106-residue spectrin repeat was thus numbered residue 5 in our previous work.

	Comment	Model protein	Mutation created in model	Helix, position, exposurea	Change in free energy of unfolding on mutation (ΔΔGD−N, kcal.mol−1)
Disease-associated SNPs
G151D (α-spectrin)	Replacement of Gly by charged residue	R16	G101D	C, end, buried	1.3 ± 0.3
L207P (α-spectrin)	Replacement of hydrophobic residue by Pro	R15	I51P	B, mid, buried	Unfolded (> 6.4)
		R16	L51P		Insoluble (> 6.1)
		R17	F51P		1.3 ± 0.4
L260P (α-spectrin)	Replacement of hydrophobic residue by Pro	R15	L104P	C, end, buried	2.3 ± 0.4
		R16	L104P		1.5 ± 0.4
		R17	L104P		0.7 ± 0.3
S261P (α-spectrin)	Replacement of polar residue by Pro	R15	N105P	C, end, surface	1.3 ± 0.4
		R16	E105P		1.2 ± 0.4
		R17	D105P		2.4 ± 0.3
Q471P (α-spectrin)	Replacement of polar residue by Pro	R15	K103P	C, end, surface	1.4 ± 0.4
		R16	R103P		2.0 ± 0.3
		R17	K103P		3.6 ± 0.3
H469P (α-spectrin)	Replacement of polar residue by Pro	R15	R101P	C, end, surface	3.2 ± 0.3
		R16	G101P		1.4 ± 0.3
		R17	K101P		4.1 ± 0.4
D791E (α-spectrin)	Replacement of acidic residue by another acidic residue	R15	E106D	C, end, surface	0.0 ± 0.3
		R16	E106D		0.3 ± 0.3
		R17	E106D		0.6 ± 0.4
Non-disease-associated SNPs
I809V (α-spectrin)	Replacement of hydrophobic residue by smaller hydrophobic	R16	I18Vb	A, mid, buried	1.4 ± 0.3
		R17	I18Vc		1.3 ± 0.4
N438S (β-spectrin)	Replacement of polar residue by smaller polar	R17	N19S	A, mid, surface	0.3 ± 0.3
H1373R (β-spectrin)	Replacement of polar residue by charged	R16	R103H	C, end, surface	0.4 ± 0.4
Q2937R (dystrophin)	Replacement of polar residue by charged	R17	Q5R	A, start, surface	0.5 ± 0.3

^aBuried residues have a side chain with a solvent-accessible surface area < 10%.

^bData taken from ⁴¹.

^cData taken from ⁴².