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

Journal of Genetic Engineering and Biotechnology

Table 3 Effects of epitopic missense variants on TNFA-certolizumab pegol 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	–	− 269.69
WT	–	–	–	–	–	L	–	− 152.18
rs1298153213	45	D>N	− 0.619	0.95	0.61	H	0.98	− 277.93
rs1298153213	–	–	–	–	–	L	0.46	− 152.11
rs373646181	85	V>F	− 1.58	0.01	0.7	H	0.97	− 271.68
rs373646181	–	–	–	–	–	L	0.54	− 152.18
rs778731236	85	V>G	0.416	1.55	0.99	H	1.08	− 266.54
rs778731236	–	–	–	–	–	L	0.47	− 152.18
rs373646181	85	V>I	0.339	0.53	0.79	H	1.01	− 274.09
rs373646181	–	–	–	–	–	L	0.48	− 152.17
rs376368223	131	R>Q	− 0.078	0.94	2.31	H	2.52	− 236.86
rs376368223	–	–	–	–	–	L	0.57	− 152.06
rs777545571	135	E>G	0.784	0.67	2.25	H	1.03	− 269.49
rs777545571	–	–	–	–	–	L	1.98	− 145.12
rs758189183	135	E>K	1.119	0.67	1.86	H	0.92	− 279.21
rs758189183	–	–	–	–	–	L	1.74	− 157.25
rs770509340	138	R>Q	0.026	2.25	1.77	H	0.41	− 269.36
rs770509340	–	–	–	–	–	L	1.96	− 120.82
rs141307820	138	R>W	0.652	1.53	2.19	H	0.51	− 269.49
rs141307820	–	–	–	–	–	L	2.42	− 142.18
rs370893734	140	D>N	0.64	0.75	0.64	H	0.42	− 269.56
rs370893734	–	–	–	–	–	L	0.88	− 147.77
rs370893734	140	D>Y	− 0.122	0.25	0.92	H	0.74	− 269.58
rs370893734	–	–	–	–	–	L	1.21	− 149.7

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