Missense variants in the TNFA epitopes and their effects on interaction with therapeutic antibodies—in silico analysis

Journal of Genetic Engineering and Biotechnology

Table 2 Effects of epitopic missense variants on TNFA-adalimumab interaction

SNP_ID	Amino acid position^a	Amino acid change	∆∆G (Kcal/mol)^b			Antibody chains	MutaBind^b	PPcheck
SNP_ID	Amino acid position^a	Amino acid change	mCSM-PPI2	SAAMBE-3D	MutaBind	Antibody chains	∆∆G (kcal/mol)	Total stabilizing energy (kJ/mol)
WT	–	–	–	–	–	H	–	− 58.31
WT	–	–	–	–	–	L	–	− 222.88
rs1454071630	66	G>C	1.345	0.38	1.94	H	1.65	− 58.09
rs1454071630	–	–	–	–	–	L	2.33	− 208.55
rs1454071630	66	G>S	1.279	0.45	2	H	1.6	− 58.05
rs1454071630	–	–	–	–	–	L	2.38	− 207.41
rs552363141	72	T>N	0.116	0.15	0.12	H	0.7	− 58.33
rs552363141	–	–	–	–	–	L	0.46	− 222.89
rs946653352	72	T>P	0.107	0.19	0.64	H	1.35	− 58.32
rs946653352	–	–	–	–	–	L	1.23	− 222.89
rs758652888	73	H>Q	0.373	0.36	0.13	H	0.9	− 58.33
rs758652888	–	–	–	–	–	L	0.63	− 222.93
rs753130938	73	H>R	0.101	0.25	0.21	H	0.94	− 58.33
rs753130938	–	–	–	–	–	L	0.66	− 222.93
rs1473587140	110	E>K	0.17	1.64	0.86	H	1.23	− 58.13
rs1473587140	–	–	–	–	–	L	1.19	− 225.92
rs760036765	111	A>T	–0.272	0.21	0.97	H	0.96	− 58.25
rs760036765	–	–	–	–	–	L	1.16	− 225.75
rs777545571	135	E>G	0.235	0.59	0.48	H	1.22	− 58.53
rs777545571	–	–	–	–	–	L	1.03	− 229.29
rs758189183	135	E>K	0.048	0.55	0.3	H	1.03	− 58.47
rs758189183	–	–	–	–	–	L	0.84	− 227.42
rs763621932	141	Y>S	0.28	1.07	1.02	H	1.16	− 58.3
rs763621932	–	–	–	–	–	L	1.3	− 217.37

^aAmino acid positions were calculated excluding the signal peptide (76 amino acids)
^bPositive values of ∆∆G indicate decreasing affinity