Table 1.
Ligand–protein interaction profiles of the selected CYP3A4 inhibitors within the CYP3A4 binding site.
| CYP3A4 Inhibitors | Autodock Energy (kcal/mol) | van der Waals Interactions Before MD | Hydrogen Bond Interactions in the Docked Poses | van der Waals Interactions in Centroid Structure from Clustering | Hydrogen Bond Interactions in the Centroid Structures | van der Waals Interactions after MD | Hydrogen Bond Interactions at 50 ns | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Acceptor Atom | Donor Atom | Distance Å | Acceptor Atom | Donor Atom | Distance Å | Acceptor Atom | Donor Atom | Distance Å | |||||
| CYP3A4-YK1 | −9.9 | Leu482, Thr309, Phe304, Asp76, Thr224, Arg372, Leu373, Arg375 | Lig: Sulphonyl=O3 Lig: Carbonyl=O10 |
Arg212-NH1 Arg105-NE |
3.01 2.93 |
Phe220, Gly109, Pro107, Leu373, Tyr53, Thr224, Glu374, Gly481, Ala370, Leu482, Arg212 | Arg372=O Lig: Carbonyl=O3 Lig: Carbonyl=O3 |
Lig: Hydroxyl-O2 Arg105-NE Glu374-NH |
2.62 3.68 3.70 |
Tyr53, Arg105, Arg106, Pro107, Gly109, Phe213, Leu216, Phe220, Ala370, Leu373, Gly481, Leu482 | Arg372=O Lig: Carbonyl=O3 |
Lig: Hydroxyl-O2 Glu374-NH |
2.58 3.05 |
| CYP3A4-YK2 | −11.6 | Phe316, Glu308, Gln484, Thr309, Phe304, Phe108, Arg105, Phe213, Glu374, Gly481, Leu482, Leu483 | Ser312-OG Ala370=O Arg372=O |
Lig: Hydroxyl-O Lig: Hydroxyl-O2 Lig: Hydroxyl-O2 |
3.01 2.81 3.13 |
Ser312, Glu308, Arg212, Thr309, Phe304, Phe108, Arg105, Phe57, Glu374, Leu373, Leu483, Gln484 | Arg372=O | Lig: Hydroxyl-O2 | 2.71 | Phe57, Arg105, Arg212, Phe304, Thr309, Ser312, Leu373, Glu374, Leu462, Gln484 |
Arg372=O | Lig: Hydroxyl-O2 | 2.96 |
| CYP3A4-YK3 | −9.5 | Phe57, Arg105, Arg106, Phe108, Ala305, Phe304, Thr309, Met371 | Lig: Sulphonyl=O2 Lig: Carbonyl=O1 Lig: Carbonyl=O1 Lig: Carbonyl=O1 |
Arg212-NH1 - Ser119-OG Arg212-NH1 Arg212-NH2 |
3.05 3.53 3.18 3.02 |
Ile50, Tyr53, Asp76, Leu216, Leu221, Thr224, Val225, Gly481, Leu482, Arg212, Ala370, Leu373 |
Lig: Sulphonyl=O1 Lig: Hydroxyl-O3 Lig: N2 |
Arg106:NE Arg105:NH1 Arg372:NH |
3.11 3.20 3.50 |
Asp76, Ile47, Arg105, Phe215, Leu216, Phe220, Leu221, Thr224, Ala370, Leu373, Glu374, Leu482 | No hydrogen bonds formed | No hydrogen bonds formed | -- |
| CYP3A4-YK4 | −11.7 | Phe108, Thr309, Phe304, Glu308, Ser312, Phe316, Leu373, Met371, Leu482, | Ser312-OG Leu483=O |
Lig: Amine-N5 Lig: Amine-N5 |
3.16 3.12 |
Ser312, Gln484, Leu482, Thr309, Asp214, Phe316, Leu483, Pro485, Pro368, Met371, Ala370, Phe108, Ser119, Arg105 | Phe213=O Arg212-NE Arg212-NH1 |
Lig: Amine-N2 Lig: Amine-N3 Lig: Amine-N3 |
3.22 3.64 3.66 |
Phe57, Arg106, Phe215, Phe241, Ile301, Pro368, Ala370, Glu374, Gly480, Gly481, Leu482 | Ser119-O | Lig: Hydroxyl-O1 | 2.96 |
| CYP3A4-YK5 | −10.4 | Arg105, Arg106, Ser119, Phe241, Ile301, Phe215, | Glu374-OE2 Lig: Carbonyl=O3 |
Lig: Hydroxyl-O Arg212-NH1 |
3.32 3.13 |
Phe316, Ile369, Leu483, Met371, Arg372, Phe215, Glu374, Ser312, Gln484, Glu308, | Lig: Carbonyl=O Ala349=O Lig: Carbonyl=O1 |
Leu483-NH Lig: Amine-N2 Arg212:NH1 |
2.82 3.38 2.91 |
Arg105, Ser119, Phe304, Gly306, Glu308, Ser312, Phe316, Ile369, Ala370, Met371, Gln484, Pro485 | Thr309-OG1 Lig: Carbonyl=O |
Lig: Hydroxyl-O3 Leu483-N |
2.77 3.00 |
The terms MD and Lig are used as an abbreviation for Molecular Dynamics and Ligand respectively in Table 1.