Computational re-engineering of Amylin sequence with reduced amyloidogenic potential

BMC Structural Biology

Table 3 Amylin Mutations generated by FibrilMutant with destabilizing potential

Original	Residue no.	Mutated	Disruption	TANGO
amino acid		amino acid	method	rank
A	13	R	Making core charged	1
F	15	P	Mutating an amino acid on a beta strand	2
F	15	D	Making core charged	3
L	16	D	Making core charged	4
A	25	R	Making core charged	5
I	26	R	Making core charged	6
G	24	P	Mutating GLY at a turn	7
L	27	R	Making an amino acid on a beta strand charged	8
F	23	E	Making core charged	9
G	24	D	Making core charged	10
V	17	E	Making core charged	11
Q	10	H	Making protein surface hydrophobic	12
N	21	P	Mutating an amino acid at a turn	14
C	2	Q	Making protein surface hydrophobic	15
T	6	M	Making protein surface hydrophobic	16
T	4	S	Making protein surface hydrophobic	17
V	32	K	Making an amino acid on a beta strand charged	18
N	3	H	Making protein surface hydrophobic	19
A	8	E	Making an amino acid on a beta strand charged	20
T	9	N	Making protein surface hydrophobic	21
L	12	E	making core charged	23
C	7	T	Making protein surface hydrophobic	24
G	33	E	Making an amino acid on a beta strand charged	25
S	20	G	Discovered experimentally [29]	13
S	20	K	Discovered experimentally [29]	22
N	21	L	Discovered experimentally [56]	26
N	14	L	Discovered experimentally [56]	27

Mutations above the horizontal line are destabilizing mutations proposed by FibrilMutant, and mutations below the line have been suggested and tested experimentally. Mutations are ranked by TANGO from lowest aggregation potential to highest aggregation potential.

ISSN: 1472-6807