TABLE 7.

Bond and binding site of highly active compounds against different targets including KOR, DOR, KAS, DHFR, GLR, URO, BCL-2, EGFR, COX-2, and TNF-α.

Receptor	Compounds	Biniding affinites (kcal/mol)	Bond type	Amino acids
KOR	C8	−5.7	Pi- sigma	Leu 107
			Pi-Pi	Tyr 140
			Alkyl	Ile 137, Trp 183
	C9	−5.8	Pi-Alkyl	Leu 107, Ile 137, TRP 183
	C14	−5.7	Pi- sigma	Trp 183
			Alkyl	Phe 99, Leu 103, Leu 107, Ile 133, Ile 137, Tyr 140
	C19	−6.9	Alkyl	Leu 107, Ile 133, Ile 137, Tyr 140, TRP 183
	Loperamide	−7.7	Pi- Sigma	Ile 180
			Alkyl	Tyr 140, Trp 183
DOR	C2	−7	Pi- Alkyl	Leu 69, Val 70, Ala 319, Cys 328
	C4	−7	Alkyl	Leu 69, Val 70, Pro 315, Ala 319, Phe 325, Cys 328, Phe 329, Leu 332
	C8	−7	Alkyl	Leu 69, Val 70, Phe 72, Cys 328, Phe 329, Leu 332
	C37	−7	Alkyl	Leu 69, Val 70, Val 316, Ala 319, Phe 325, Cys 328, Phe 329, Leu 332
	Loperamide	−8.9	Alkyl	Leu 69, Ala 319, Cys 328, Phe 329
			Pi- Sigma	Val 62, Leu 69, Val 316
			Carbon-hydrogen bond	Pro 315
			Conventional Hydrogen Bond	Gly 66
KAS	C12	−6.3	Alkyl	Trp 32, Val 212, Ala 216, Leu 220, Ala 246, Ile 250
			Carbon-hydrogen bond	Gly 209
			Conventional Hydrogen Bond	Asn 247
			Halogen(Fluorine)	Gly 152
	C19	−6.8	Conventional Hydrogen Bond	Leu 189
			Alkyl	Ala 111, Leu 191
	C21	−6.3	Alkyl	Trp 32, Ile: 156, Leu 189, Met 207, Val 212, Phe 213, Ala 216, Ala 246, Ile 250, Phe 304
	C23	−6.4	Conventional Hydrogen Bond	Asn 247, Arg 249
			Alkyl	Trp 32, Leu 189, Val 212, Phe 213, Ala 246, Ile 250
	Amoxicillin	−7.1	Conventional Hydrogen Bond	Arg 36, Ala 246
			Alkyl	Val 212
			Pi- Sigma	Met 207
			Unfavorable Donor- Donor	Asn A:247
DHFR	C8	−6.1	Pi-Pi T-shaped	Tyr 121
			Pi-Alkyl	Ile 16, Leu 22
	C9	−6.4	Conventional Hydrogen Bond	Ser 119
			Alkyl	Leu 75
			Pi- Carbon	Arg 77
	C18	−6.1	Van der waals	Asp 21
			Carbon-hydrogen bond	Gly 17
			Amide-Pi-Stacked	Gly 20
			Alkyl	Ala 9, Ile 16, Lys 55
	C19	−7.4	Pi- Sigma	Leu 22
			Alkyl	Ile 16
	C23	−6.3	Conventional Hydrogen Bond	Ser 118
			Alkyl	Val 8, Ala 9, Ile 16, Phe 34, Lys 55, Tyr 121
	Ciprofloxacin	−7.6	Conventional Hydrogen Bond	Glu 30, Ser 118
			Carbon-hydrogen bond	Tyr 121
			Pi- Sigma	Leu 22
			Alkyl	Ala 9, Ile 16
GLR	C12	−6.2	Alkyl	Lys 53, Ala 342
			Carbon-hydrogen bond	Thr 339
			Conventional Hydrogen Bond	Ser 30, Gly 31, Thr 57, Cys 58, Asp 331
	C18	−6.9	Alkyl	Cys 58, Lys 66, Ile 198, Arg 291, Leu 337
			Conventional Hydrogen Bond	Cys 63, Tyr 197
			Amide-Pi-Stacked	Gly 62
	C19	−7	Van der waals	Thr 369
			Amide-Pi-Stacked	Pro 368
			Pi- Alkyl	Leu 338, Val 370, Phe 372
	C23	−7.3	Conventional Hydrogen Bond	Cys 63
			Pi-Pi	Gly 62, Tyr 197
			Alkyl	Cys 58, Lys 66, Ile 198, Arg 291, Leu 337, Ala 291
	Ascorbic acid	−6.4	Unfavorable Donor- Donor	Cys 58
			Conventional Hydrogen Bond	Ser 30, Gly 31, Val 329, Asp 331
URO	C8	−5.7	Alkyl	Leu 170, Arg 176, His 256
	C9	−5.7	Conventional Hydrogen Bond	Tyr 257
			Alkyl	Arg 176, His 256
	C18	−5.4	Conventional Hydrogen Bond	Arg 176
			Alkyl	Leu 170, Lys 171, Phe 278
			Pi- Sigma	Phe 258
			Pi- Donor Hydrogen Bond	His 256
	C19	−6.8	Pi-Alkyl	Arg 176
			Pi- Sigma	phe 258
			Pi- Anion	Glu 259
	Ascorbic acid	−5.3	Conventional Hydrogen Bond	Arg 176, Ile 177, Asn 254, Tyr 257
BCL-2	C2	−6.3	Pi-Pi T-shaped	Phe 101
			Pi-Alkyl	Met 112, Ala 146
	C9	−6.4	Conventional Hydrogen Bond	Asp 108
			Pi- Sigma	Met 112
			Alkyl	Phe 101
	C19	−6.7	Pi-Alkyl	Phe 101, Leu 134
	C21	−6.3	Alkyl	Phe 101, Tyr 105, Phe 109, Met 112, Val 130, Leu 134, Ala 146
	C23	−6.6	Pi- Sigma	Tyr 105, Leu 134
			Alkyl	Phe 101, Met 112, Ala 146
	Lapatinib	−8.4	Pi- Action	Asp 108
			Pi-Pi T-shaped	Tyr 105
			Alkyl	Met 112, Leu 134
EGFR	C12	−7.1	Conventional Hydrogen Bond	Thr 790, Asp 855
			Halogen(Fluorine)	Met 766, Cys 775, Arg 776, Thr 854, Phe 856
			Alkyl	Leu 718, Val 726, Ala 743, Lys 745, Leu 844
	C19	−7.8	Unfavorable Aceptor- Aceptor	Asp 855
			Pi- Sigma	Val 726
			Alkyl	Leu718, Cys 797, Leu 844
	C21	−7	Pi- Sigma	Phe 856
			Alkyl	Leu 718, Val 726, Ala 743, Lys 745, Met 766, Cys 775, Leu 777, Leu 788, Leu 844
	C23	−7.4	Conventional Hydrogen Bond	Cys 797
			Pi- Sigma	Leu 844
			Alkyl	Leu 718, VAl 726, Ala 743, Lys 745, Tyr 998, Leu 1001, Met 1002
	Lapatinib	−10.6	Conventional Hydrogen Bond	Thr 790
			Pi- Carbon	Lys 745
			Halogen(Fluorine)	Cys 775, Arg 776
			Carbon-hydrogen bond	Ser 720, Asp 855
			Pi- Sigma	Met 766
			Pi-Pi T-shaped	Phe 856
			Alkyl	Leu 718, Val 726, Ala 743, Leu 777
COX-2	C9	−7.3	Conventional Hydrogen Bond	Val 523
			Amide-Pi-Stacked	Gly 526
			Alkyl	Val 349, Leu 352, Trp 387, Ala 527
	C14	−7.2	Conventional Hydrogen Bond	Arg 513
			Carbon-hydrogen bond	His 90, Ser 353
			Alkyl	Val 349, Leu 352, Leu 359, Phe 518, Val 523, Ala 527, Leu 531
	C18	−7.4	Carbon-hydrogen bond	Ala 527, Ser 530
			Amide-Pi-Stacked	Gly 526
			Pi- Sulfur	Met 522
			Alkyl	His 90, Met 113, Val 116, Leu 117, Val 349, Leu 359, Ala 516, Val 523, Leu 531
	C19	−7.9	Pi- Sigma	Val 349
			Alkyl	Val 116, Val 523, Val 527, Leu 531, Leu 352
	C21	−7.2	Alkyl	Met 113, Val 116, Tyr 348, Val 349, Leu 352, Tyr 355, Leu 359, Trp 387, Phe 518, Met 522, Val 523, Ala 527, Leu 531
	C23	−7.8	Carbon-hydrogen bond	Ala 527, Ser 530
			Pi- Sulfur	Met 522
			Amide-Pi-Stacked	Gly 526
			Alkyl	His 90, Val 116, Val 349, Leu 352, Leu 359, Ala 516, Leu 531, Val 523
	Diclofenac	−7.8	Conventional Hydrogen Bond	Tyr 355
			Pi- Sigma	Val 349, Ala 527
			Amide-Pi-Stacked	Gly 526
			Alkyl	Leu 352, Leu 531
TNF-α	C8	−6.5	Conventional Hydrogen Bond	Gly 121
			Pi- Sigma	Tyr 59
			Alkyl	Leu 57, Tyr 119
	C9	−6.7	Conventional Hydrogen Bond	Gly 121
			Carbon-hydrogen bond	Tyr 59
			Alkyl	Leu 57, Tyr 119
	C18	−6.3	Carbon-hydrogen bond	Gly 121
			Alkyl	Leu 57, Tyr A 59, Tyr B 59,
	C19	−7.4	Pi-Pi-Stacked	Tyr 59
			Alkyl	Leu A 57, Leu 57, Tyr 59
	C23	−6.5	Carbon-hydrogen bond	Gly 121
			Pi- Sigma	Tyr 59
			Alkyl	Leu 57, Tyr 59, Tyr 119
	Diclofenac	−7.1	Conventional Hydrogen Bond	Leu 120
			Pi-Pi-Stacked	Tyr 59, Tyr 119