Table 2.
Summary of comparative binding interaction analysis of aspirin, rofecoxib, AGP, and hit AGP analogs A1–7 with AF-COX-2 protein.
| Compounds Name | Interacting amino acids | H-bond (distance) with interacting site | HYD bond (distance) with interacting site |
|---|---|---|---|
| Aspirin | Val335, Leu338, Ser339, Trp373, Phe504, Met508, Val509, Gly512, Ala513, Ser516 | Ser516 (3.97 Å) [COOH group] |
Leu338 (4.50 Å) [benzene ring], Met508 (6.33 Å) [Benzene ring], Val509 (4.59 Å) [Benzene ring] |
| Rofecoxib | His75, Leu78, Met99, Val102, Arg106, Ile331, Val335, Tyr341, Leu345, Leu338, Ser339, Arg499, Phe504, Val509, Ala513, Leu517 | Arg499 (6.43 Å) [5-one(furan ring)] |
Val102 (6.06) [Sulphonylphenyl Moiety], Val335 (6.38 Å) [Sulphonylphenyl Moiety], Leu345 (5.68 Å) [Phenyl Moiety], Val509 (4.57 Å) [Phenyl Moiety], Ala513 (5.11 Å) [Phenyl Moiety], Leu517 (6.75 Å) [Sulphonylphenyl Moiety] |
| AGP | Leu78, Met99, Val102, Arg106, Val335, Leu338, Ser339, Tyr341, Leu345, Arg499, Phe504, Met508, Val509, Gly512, Ala513, Ser516 |
Ser516 (4.05 Å) [2-one (oxolane Moiety)], Met508 (4.99 Å) [Oxolane Moiety], Val509 (2.83 Å) [4-hydroxy (oxolane Moiety)] |
Val102 (4.43 Å) [5-methyl], Arg106 (4.40 Å) [5-methyl], Val335 (5.36 Å) [Naphthalene moiety], Tyr341 (4.60 Å; 5.60 Å; 6.48 Å) [Naphthalene moiety], Leu345 (5.33 Å; 6.14 Å) [Naphthalene moiety], Phe504 (5.79 Å) [2-methylidene], Val509 (4.48 Å; 5.33 Å) [Naphthalene moiety] |
| A1 | Pro71, Val74, His75, Leu78, Arg106, Val335, Leu338, Ser339, Tyr341, Leu345, Trp373, Arg499, Phe504, Met508, Val509, Glu510, Gly512, Ala513, Ser516, Leu517 |
Arg106 (6.44 Å) [4-hydroxy-oxolane], Val509 (2.84 Å) [6-hydroxy], Glu510 (4.69 Å) [4-hydroxy-oxolane] |
Val335 (4.53 Å; 5.47 Å) [Naphthalene moiety], Leu338 (5.24 Å) [8a-methyl], Leu345 (5.39 Å) [8a-methyl], Phe504 (6.05 Å) [Naphthalene moiety], Val509 (3.35 Å) [Naphthalene moiety], Ala513 (3.49 Å; 4.61 Å; 4.92 Å) [Naphthalene moiety] |
| A2 | Val102, Arg106, Val335, Leu338, Ser339, Tyr341, Leu345, Tyr371, Trp373, Arg499, Phe504, Met508, Val509, Gly512, Ala513, Ser516, Leu517 |
Arg106 (3.68 Å) [6-hydoxy naphthalene], Met508 (3.66 Å) [4-hydroxy oxolane], Ala513 (4.06 Å) [4-hydroxy oxolane], Ser516 (4.30 Å) [Oxolane moiety] |
Val102 (4.44 Å) [5-methyl], Val335 (5.10 Å; 5.46 Å) [8a-methyl; Naphthalene moiety], Tyr341 (5.39 Å; 5.85 Å; 6.99 Å) [8a-methyl; 2-methylidene; Naphthalene moiety], Leu345 (5.50 Å) [8a-methyl], Phe504 (5.79 Å) [2-methylidene], Val509 (4.32 Å; 4.94 Å) [2-methylidene; Naphthalene moiety], Ala513 (4.81 Å; 5.39 Å) [Naphthalene moiety] |
| A3 | Met99, Val102, Arg106, Val335, Leu338, Ser339, Tyr341, Leu345, Tyr371, Trp373, Arg499, Phe504, Met508, Val509, Gly512, Ala513, Ser516, Leu517 | Tyr371 (5.81 Å) [Oxolane moiety] |
Val102 (4.35 Å) [5-methyl], Val335 (5.07 Å; 5.41 Å) [8a-methyl; Naphthalene moiety], Tyr341 (5.36 Å; 5.90 Å; 7.01 Å) [8a-methyl; 2-methylidene; Naphthalene moiety], Leu345 (5.64 Å) [8a-methyl], Phe504 (5.74 Å) [2-methylidene], Val509 (4.15 Å; 4.82 Å) [2-methylidene; Naphthalene moiety], Ala513 (4.80 Å; 5.37 Å) [Naphthalene moiety] |
| A4 | Met99, Val102, Arg106, Val335, Leu338, Ser339, Tyr341, Leu345, Trp373, Arg499, Phe504, Met508, Val509, Gly512, Ala513, Ser516, Leu517 |
Met508 (3.73 Å) [4-hydroxy oxolane], Ala513 (4.01 Å) 4-hydroxy oxolane], Ser516 (4.45 Å) [Oxolane moiety] |
Val102 (4.35 Å) [5-methyl], Val335 (5.17 Å; 5.38 Å) [8a-methyl; Naphthalene moiety], Tyr341 (5.20 Å; 5.84 Å; 6.90 Å) [8a-methyl; 2-methylidene; Naphthalene moiety], Leu345 (5.56 Å) [8a-methyl], Phe504 (5.74 Å) [2-methylidene], Val509 (4.22 Å; 4.92 Å) [2-methylidene; Naphthalene moiety], Ala513 (4.93 Å) [Naphthalene moiety] |
| A5 | Val74, His75, Leu78, Arg106, Val335, Leu338, Ser339, Tyr341, Leu345, Trp373, Arg499, Phe504, Met508, Val509, Glu510, Gly512, Ala513, Ser516, Leu517 |
Arg106 (5.76 Å) [6-hydoxy naphthalene], Arg499 (6.55 Å) [5-one(furan ring)], Met508 (3.91 Å) [6-hydroxy naphthalene], Ala513 (3.86 Å) [6-hydroxy naphthalene] |
Val335 (4.32 Å; 5.20 Å; 5.24 Å; 5.85 Å) [2-methylidene; Naphthalene moiety], Leu338 (4.81 Å; 5.86 Å) [5 and 8a-methyl], Leu345 (5.60 Å) [2-methylidene] Val509 (4.70 Å) [Naphthalene moiety], Ala513 (4.27 Å; 4.39 Å) [Naphthalene moiety], Leu517 (6.06 Å; 7.03 Å) [2-methylidene; Naphthalene moiety] |
| A6 | Leu78, Val102, Arg106, Tyr334, Val335, Leu338, Ser339, Tyr341, Leu345, Tyr371, Trp373, Phe504, Met508, Val509, Gly512, Ala513, Ser516, Leu517 | – |
Leu78 (5.95 Å) [10b-methyl], Val335 (4.92 Å; 5.76 Å) [Naphthalene], Leu338 (4.52 Å; 5.72 Å) [8-methylidene; naphthalene], Tyr341 (5.75 Å, 5.99 Å) [10b-methyl; 1,3-dioxin], Leu345 (6.49 Å) [1,3-dioxin], Phe504 (5.01 Å; 7.52 Å) [8-methylidene; naphthalene], Val509 (3.68 Å; 3.86 Å; 4.93 Å) [8-methylidene; 6a-methyl; naphthalene], Ala513 (3.60 Å; 3.95 Å; 4.09 Å) [6a-methyl; naphthalene] |
| A7 | Leu78, Val102, Arg106, Tyr334, Val335, Leu338, Ser339, Tyr341, Leu345, Tyr371, Trp373, Phe504, Val509, Gly512, Ala513, Ser516, Leu517 | – |
Leu78 (5.85 Å) [10b methyl], Val335 (5.80 Å) [Naphthol], Leu338 (4.39 Å) [8-methylidene], Tyr341 (5.91 Å) [10b methyl], Phe504 (5.24 Å) [8-methylidene], Val509 (3.94 Å; 4.00 Å; 5.20 Å) [8-methylidene; 6a-methyl; naphthalene], Ala513 (3.62 Å; 4.10 Å; 6.26 Å) [6a-methyl; naphthol] |
H bond, Hydrogen bond; HYD, Hydrophobic.