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

Journal of Genetic Engineering and Biotechnology

Table 4 Effects of epitopic missense variants on TNFA-golimumab 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	–	− 290.62
WT	–	–	–	–	–	L	–	− 55.79
rs140654183	105	T/N	0.463	0.67	0.84	H	0.58	− 294.29
rs140654183	–	–	–	–	–	L	0.98	− 56.15
rs760036765	111	A/T	− 0.711	0.54	1.35	H	1.62	− 300.47
rs760036765	–	–	–	–	–	L	1.01	− 55.71
rs770509340	138	R/Q	0.075	1.47	0.49	H	0.25	− 284.33
rs770509340	–	–	–	–	–	L	0.96	− 54.37
rs141307820	138	R/W	0.668	1.03	0.72	H	0.44	− 285.08
rs141307820	–	–	–	–	–	L	1.23	− 55.81
rs370893734	140	D/N	1.279	0.96	2.4	H	0.75	− 293.72
rs370893734	–	–	–	–	–	L	1.41	− 62.05
rs370893734	140	D/Y	0.213	0.78	4	H	1.01	− 285.94
rs370893734	–	–	–	–	–	L	1.42	− 53.07
rs763621932	141	Y/S	2.219	1.34	2.45	H	2.07	− 270.91
rs763621932	–	–	–	–	–	L	1.43	− 55.23

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