Table 1.

Experimental binding affinities of selected ligands

No. of atoms	Ligand	Target	Type*	−log K1†	Ref.
1	Ca2+	Amino transferase	IM	6.70	5
1	Hg2+	Uroporphy synthase	IM	6.00	5
1	Mn2+	Inositol phosphatase	IM	5.70	5
1	Fe3+	Hydroxylase	IM	5.30	5
1	Ag+	Arylformamidase	IM	5.00	5
1	F−	Phosphotransferase	IA	4.55	5
1	S2−	Peroxidase	IA	4.28	5
1	Xe	Myoglobin	L	2.30	6
1	NH3	Meamine glutamate transferase	I	1.79	5
2	Carbon monoxide	Myoglobin	L	7.52	7
2	Oxygen	Myoglobin	L	6.18	7
2	Cyanide	Methane oxygenase	IA	6.00	5
2	Hydroxylamine	Glycerol oxidase	IC	5.92	5
3	Azide	Glycerol oxidase	IA	5.70	5
3	Ethylamine	Protease I	I	3.00	5
4	Thioacetamide	Methane monooxygen	I	5.00	5
4	NO3−	Carbonate deydratase	IA	4.70	5
4	Vanadate	Phytase	IA	4.55	5
5	Thiosemicarbazide	Methane monooxygen.	I	6.00	5
5	SO42−	Creatine kinase	IA	5.22	5
5	Iodoacetamide	Methyl transferase	IC	5.00	5
6	Putrescine	Spermine synthase	I	8.77	5
6	Aminooxyacetic acid	Aminotransferase	I	7.19	5
6	Oxalate	Lactate dehydrogenase	IA	5.80	5
7	α-Aminobutyid acid	Neuromanidase transmitter	L	8.00	2
7	l-Cysteine	Serine acetyl transferase	I	6.22	5
7	Aminomethiozolidine	Methyl transferase	I	5.40	5
8	Muscimol	α-aminobutylicacid agonist	L	8.73	2
8	Bromopyrimidone	Cytosine deaminase	I	6.24	5
8	Phosphonoacetic acid	DNA polymerase	I	6.00	5
9	Acetopyruvate	Acetoacetate decarboxylase	I	7.00	5
9	Methyl iodotyrosine	Tyrosine monooxygenase	I	6.30	5
9	Nitrooxazolidinone	Aldehyde dehydrogenase	I	5.46	5
9	Benzamidine	Trypsin	I	4.77	8
10	Allopurinol	Xanthine oxidase	I	9.17	2
10	Acetylcholine	Cholinergic receptor	L	8.14	2
10	Cabachol	Cholinergic receptor	L	7.85	2
11	Diethyl pyrocarbonate	Ca2+ transmitter	L	8.80	5
11	Dopamine	α, β-androgen receptor	L	8.65	2
11	Mercapto oxoglutaric	Isocitrate dehydrogenase	I	8.30	5
12	Norepinephrine	Adrenergic agonist	L	8.88	2
12	Nicotine	Nicotinic receptor	L	8.22	2
12	Hydroxybenzyl-Me3NR4	Acetycholiesterase I	I	7.68	5
13	Tiamenidine	α-Adrenergic agonist	L	8.66	2
13	Serotonin	5-Hydroxy tryptamine receptor	L	8.30	9
13	Benzyl mercaptopropionate	Carboxypeptidase	I	7.96	5
14	Guanabenz	α-Adrenergic receptor	L	9.02	2
14	Methylenpenicillanic	β-Lactamase	I	8.85	5
14	Captopril	Carboxypeptidase	I	8.70	5
15	Aminoclonidine		L	9.32	2
15	Guanfacine	α-Adrenergic agonist	L	8.73	2
15	Isatin derivative	Rhino protease	I	7.30	10
16	Acetophenone der.	ACEsterase	IC	14.89	11
16	Biotin	Streptavidin	L	13.43	8
16	Naphazoline	Adrenergic	L	8.73	2
17	Melatonin	Melatonin receptor	L	8.96	12
17	Guanine derivative	Purine nucleoside phosphorylase	I	7.96	4
17	piperoxan	antihyper. receptor	L	7.85	2
18	Iodomelatonin	Melanin receptor	L	10.68	12
18	Alprenolol	β-adrenergic receptor	L	9.47	2
18	Phosphoramidon	Metalloproteinase	I	7.55	5
19	Vesamicol	Vesamicol receptor	L	9.47	13
19	Propranolol	β-adrenergic receptor	L	9.39	2
19	Trimethoprim der	Dihydrofolate reductase	I	8.53	14
20	Estradiol	Steroid receptor	L	9.69	2
20	Melatonin derivative	Melatonin receptor	L	9.68	12
20	Vesamicol derivative	Vesamicol receptor	L	9.20	13
21	2-Carboxyl arabinitol bisphosphate	Ribulose carboxylase	I	12.72	15
21	4-Carboxyl arabinitol bisphosphate	Ribulose carboxylase	I	10.55	15
21	Triprolidine	Histamine antagonist	L	9.98	2
21	Trimethoprim	dihydrofolate reductase	I	8.44	2
22	Amitriptylinoxide	Antidepressant	L	9.02	2
22	Mazindol derivative	Dopamine transporter	L	8.82	16
22	Indolyl ethyl amines	5-Hydroxy tryptamine receptor	L	8.49	17
22	Isatin derivative	Rhino protease	I	8.00	10
23	Vesamicol der.	VR	L	11.05	13
23	Neuraminic acid der.	Sialidase	I	10.52	18
23	Melatonin der.	melamin receptor	L	10.24	12
23	Vesamicol der.	VR	L	10.17	13
24	Vesamicol der.	VR	L	11.19	13
24	Isatin der.	Rhino protease	I	8.70	10
24	Methadone	Narcotic	L	8.66	2
25	Melatonin der.	Melamin receptor	L	9.62	12
25	Corticosterone	Steroid receptor	L	8.51	2
25	Isatin der.	Rhino protease	I	8.40	10
26	Aldosterone	Steroid receptor	L	9.32	2
26	Haloperidol	Antipsychotic	L	9.02	2
26	Yohimbine	α-2 adrenergic receptor	L	8.73	2
26	Isatin der.	Rhino protease	I	8.40	10
27	Vesamicol der.	VR	L	9.74	13
27	Dexetimide	Anticholinergic	L	8.80	2
27	Dehydrosinefungin	mRNA Me trans.	I	8.74	5
28	Vesamicol der.	VR	L	9.82	13
28	Indoyl ethyl amines	5-Hydroxy tryptamine receptor	L	9.70	17
28	Prazosin	α1-adrenergic agonist	L	9.62	2
29	Spiperone		L	10.27	2
29	Ketanserin	Serotonin antagonist	L	9.39	2
29	Dextromoramide	Analgesic	L	9.02	2
30	Peptide phosphonates	Carboxy peptidase	IM	12.00	19
30	Domperidone	Dopamine antagonist	L	10.13	2
30	Etorphine	Narcotic	L	9.91	2
31	Carboxamide derivative	5-Hydroxy tryptamine receptor	L	9.54	20
31	Benzodiazepine derivative	Integrin antagonist	L	8.60	21
31	Budesonide	Glucocorticoid receptor	L	8.54	22
31	Flavin mononucleotide	Cytochrome b reductase	I	8.10	5
32	Serotonin dimer	5-Hydroxy tryptamine receptor	L	9.34	9
32	Cyclic urea	HIV protease	I	8.85	23
32	Hoechst 33258	DNA	L	7.41	24
33	Methotrexate	Dihydrofolate reductase	I	9.70	8
34	Cyclic-aza isostere	HIV protease	I	10.21	25
34	Buprenorphine	narcotic	L	9.83	2
34	Pimozide	antipsychotic	L	9.39	2
34	Hoechst 33342	DNA	L	7.44	24
35	Peptide phosphonates	Carboxypeptidase	IM	11.52	19
35	Argatroban	Thrombin	I	7.72	8
35	Peptide derivative	Thermolysin	I	7.29	8
36	Cyclic-aza isostere	HIV protease	I	10.15	25
36	Benzodiazepines	Integrin	L	8.55	21
36	Cyclic urea	HIV protease	I	8.37	23
37	Peptide phosphonates	Carboxypeptidase	IM	11.40	19
37	Cyclic-aza isostere	HIV protease	I	9.31	25
37	Benzodiazepines	Integrin	L	8.80	21
38	Hydroxypyrone	HIV protease	I	10.22	26
38	Cyclic urea	HIV protease	I	9.92	23
38	Benzodiazepines	Integrin	L	8.40	21
39	Cyclic sulfone	HIV protease	I	9.52	27
39	Benzodiazepines	Integrin	L	7.05	21
40	Cyclic-aza isostere	HIV protease	I	11.30	25
40	Hydroxy pyrone	HIV protease	I	11.16	26
41	Peptide phosphonates	Carboxypeptidase	IM	12.00	19
41	Cyclic urea	HIV protease	I	9.48	23
41	Cyclic sulfone	HIV protease	I	9.22	27
42	Hydroxypyrone	HIV protease	I	11.10	26
42	Cyclic urea	HIV protease	I	9.85	23
43	Peptide phosphonates	Carboxypeptidase	IM	13.96	19
43	Cyclic urea	HIV protease	I	9.48	23
43	Cyclic sulfone	HIV protease	I	9.00	27
44	Cyclic urea	HIV protease	I	10.41	28
45	Serotonin dimer	5-Hydroxy tryptamine receptor	L	10.05	9
46	Cyclic urea	HIV protease	I	10.75	28
46	Cyclic urea	HIV protease	I	9.51	23
47	Zaragozic acid A	Squalene synthase	I	10.11	29
48	Cyclic urea	HIV protease	I	10.35	28
50	Cyclic urea	HIV protease	I	10.20	28
50	Hydroxyethyl amine derivative	Cathepsin D	I	7.85	30
51	Zaragozic acid B	Squalene synthase	I	10.54	29
51	Combichem hydroxyethyl amine derivative	Cathepsin D	I	8.05	30
52	Cyclic urea	HIV protease	I	9.37	28
54	Cyclic urea	HIV protease	I	10.57	28
54	Combichem hydroxyethyl amine derivative	Cathepsin D	I	7.23	30
55	Peptide-based	Thrombin receptor	L	7.40	31
56	Cyclic urea	HIV protease	I	10.37	28
56	Peptide-based	Thrombin receptor	L	7.92	31
58	Cyclic urea	HIV protease	I	10.96	28
60	Cyclic urea	HIV protease	I	10.80	28
62	Cyclic urea	HIV protease	I	10.62	28
64	Cyclic urea	HIV protease	I	10.07	28
64	Acetyl-CoA	Acetyl-CoA carboxylase	I	8.00	5
67	Peptide-based	Thrombin receptor	L	8.10	31
68	Stearyl-CoA	Acetyl-CoA carboxylase	I	8.89	5

I, inhibitor; IM, metal ion inhibitor potential chelator in metalloprotein; IA, small anionic inhibitor; IC, potential covalent interaction; L, ligand (agonist or antagonist). 

^*In most cases, K_i values were taken directly from the literature; however, some IC₅₀ values have been used. Although the differences are small for purposes of this paper, original publications should be consulted for accurate thermodynamic data.