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

Journal of Genetic Engineering and Biotechnology

Table 5 Effects of epitopic missense variants on TNFA-infliximab 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	–	− 188.42
WT	–	–	–	–	–	L	–	− 148.55
rs1427914441	70	P/S	0.669	1.05	0.6	H	1.18	− 180.87
rs1427914441	–	–	–	–	–	L	0.31	− 148.18
rs758652888	73	H/Q	0.264	1.03	0.18	H	0.47	− 188.4
rs758652888	–	–	–	–	–	L	1.41	− 137.66
rs753130938	73	H/R	0.034	0.84	0.31	H	0.53	− 188.38
rs753130938	–	–	–	–	–	L	1.45	− 145.3
rs140654183	105	T/N	0.315	0.62	− 0.1	H	1.09	− 186.46
rs140654183	–	–	–	–	–	L	0.66	− 148.51
rs1473587140	110	E/K	0.491	1	0.17	H	1.18	− 184.14
rs1473587140	–	–	–	–	–	L	0.63	− 148.55
rs770509340	138	R/Q	0.875	1.81	1.2	H	0.72	− 186.64
rs770509340	–	–	–	–	–	L	1.56	− 146.21
rs141307820	138	R/W	1.234	1.01	1.2	H	1.01	− 186.21
rs141307820	–	–	–	–	–	L	1.58	− 153.47
rs370893734	140	D/N	1.439	1.25	0.66	H	0.93	− 156.05
rs370893734	–	–	–	–	–	L	0.89	− 149.23
rs370893734	140	D/Y	0.398	0.6	2.03	H	1.28	− 160.89
rs370893734	–	–	–	–	–	L	1.29	− 158.06
rs763621932	141	Y/S	0.72	0.86	0.57	H	1.3	− 180.87
rs763621932	–	–	–	–	–	L	1.02	− 148.78

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