The Performance of Several Docking Programs at Reproducing Protein–Macrolide-Like Crystal Structures
Abstract
:1. Introduction
2. Results and Discussion
2.1. Self-Docking of the Twenty PDB Structures
2.2. Ligand Conformational Search
2.3. Docking of all the Conformers of Each Ligand
2.4. Comparison of AD Vina with PSOVina
2.5. Poses with Lower RMSD Values
2.6. Re-Scoring
- (a)
- With AD 4.2//Vina, 9 out of the 20 ligands overlap almost perfectly with their respective poses in the crystals (ligands 1, 3, 7, 8, 9, 10, 12, 17, and 18, RMSD overlap = 0.32–0.67 Å), 6 ligands can be superimposed moderately well with their crystalline structures, at least their cyclic moieties (RMSD overlap = 0.79–0.93), and there are four calculated structures that do not match sufficiently well (5, 11, 13, and 14, RMSD overlap = 1.04–1.10). The worst result is for ligand 19 (RMSD overlap = 2.14); we have no explanation for it, but the crystalline structure of the complex was poorly reproduced by most methods (see Table 2, Table 3, Table 4, Table 5 and Table 6).
- (b)
- Three poses that improved after re-scoring of DOCK with Amber (Table 6) showed values of RMSD overlap for 7, 15, and 19 equal to 0.87, 1.12, and 0.75, respectively (two match partially and one not sufficiently well, also by visual inspection).
- (c)
- For the six Glide poses re-scored with MM-GBSA (Table 6), the RMSD-overlap values were 1.13, 1.36, 0.69, 0.64, 0.73, and 0.67. In other words, three ligands (12, 13, and 19) were almost superimposable with their respective experimental structures, but there were two that did not match well. It is worth noting that 19/3UYK is better described by Glide (docking and re-scoring) than by AD 4.2 (docking and AD 4.2//Vina re-scoring, respectively).
3. Materials and Methods
3.1. Crystalline Complexes
3.2. Preparation of the Ligand Files
3.3. Conformer Calculations
3.4. Preparation of the Protein Files
3.5. Docking Algorithms
3.6. Calculations of RMSD Values
4. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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AD Vina | AD 4.2 | AD 3.0 | DOCK | Glide | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|
RMSD | Score | RMSD | Score | RMSD | Score | RMSD | Score | RMSD | Score | ||
1 | 1ESV | 0.25 | −10.8 | 0.60 | −8.52 | 0.62 | −10.40 | 0.33 | −67.42 | 0.37 | −7.84 |
2 | 1FKD | 0.67 | −11.3 | 0.71 | −11.10 | 0.66 | −12.38 | 1.11 | −61.33 | 1.14 | −6.95 |
3 | 1NM6 | 0.26 | −12.8 | 0.42 | −12.79 | 1.22 | −12.24 | 0.23 | −88.46 | 1.07 | −11.32 |
4 | 1NT1 | 0.65 | −13.3 | 0.49 | −13.50 | 1.99 | −6.89 | 0.20 | −85.14 | 0.79 | −9.68 |
5 | 1PKF | 0.42 | −13.7 | 1.19 | −12.73 | 1.12 | −13.67 | 0.58 | −77.96 | 1.97 | −8.32 |
6 | 1R8Q | 0.31 | −12.6 | 0.83 | −10.66 | 0.62 | −11.69 | 0.27 | −65.97 | 0.28 | −11.73 |
7 | 1UU3 | 0.48 | −11.9 | 0.97 | −11.69 | 1.00 | −12.88 | 0.84 | −84.54 | 0.61 | −10.27 |
8 | 1W96 | 0.48 | −11.7 | 0.67 | −12.03 | 0.73 | −13.92 | 0.31 | −95.40 | 0.60 | −8.86 |
9 | 2C6H | 0.30 | −11.1 | 0.59 | −9.99 | 0.65 | −12.36 | 0.70 | −79.95 | 1.27 | −6.61 |
10 | 2E9U | 0.38 | −10.2 | 0.47 | −9.10 | 0.67 | −10.20 | 0.22 | −67.52 | 0.39 | −8.68 |
11 | 2IYA | 0.49 | −13.2 | 0.50 | −11.60 | 0.40 | −14.73 | 0.73 | −84.69 | 1.39 | −9.37 |
12 | 2VWC | 0.31 | −9.4 | 1.45 | −9.15 | 0.80 | −10.43 | 0.51 | −78.13 | 1.04 | −6.94 |
13 | 2XBK | 0.62 | −18.5 | 1.50 | −15.23 | 1.05 | −18.33 | 0.66 | −115.34 | 1.05 | −11.64 |
14 | 2XX5 | 0.52 | −11.3 | 0.75 | −10.58 | 0.83 | −8.92 | 1.04 | −73.64 | 0.70 | −8.84 |
15 | 3DV1 | 0.74 | −10.9 | 1.17 | −11.57 | 0.94 | −14.29 | 0.60 | −94.39 | 1.94 | −9.25 |
16 | 3DV5 | 1.02 | −11.6 | 0.50 | −15.36 | 0.37 | −17.22 | 0.49 | −113.99 | 2.37 b | −8.20 |
17 | 3EKS | 0.91 | −11.5 | 0.58 | −11.77 | 0.73 | −12.06 | 0.35 | −75.36 | 0.35 | −10.00 |
18 | 3QTF | 0.51 | −13.3 | 0.95 | −10.88 | 1.13 | −12.57 | 0.44 | −78.45 | 0.82 | −11.53 |
19 | 3UYK | 0.97 | −10.7 | 1.26 | −10.03 | 1.39 | −10.76 | 0.79 | −55.11 | 0.63 | −7.92 |
20 | 4DRU | 0.68 | −13.1 | 1.16 | −12.99 | 1.16 | −12.92 | 0.93 | −71.69 | 1.03 | −8.78 |
mean | 0.55 ± 0.05 | 0.84 ± 0.08 | 0.90 ± 0.08 | 0.57 ± 0.06 | 0.99 ± 0.13 | ||||||
SD | 0.23 | 0.34 | 0.37 | 0.28 | 0.57 | ||||||
median | 0.50 | 0.73 | 0.82 | 0.55 | 0.93 |
No. Conf. | AD Vina | AD 4.2 | AD 3.0 | DOCK | Glide | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
RMSD | Score | RMSD | Score | RMSD | Score | RMSD | Score | RMSD | Score | |||
1 | 1ESV | 73 | 0.47 | −10.7 | 0.72 | −9.47 | 1.04 | −11.56 | 0.59 | −61.98 | 0.62 | −8.44 |
2 | 1FKD | 315 | 1.55 | −9.1 | 1.09 | −10.29 | 2.62 | −9.89 | 0.86 | −71.40 | 1.45 | −7.00 |
3 | 1NM6 | 531 | 7.85 | −10.9 | 0.89 | −12.17 | 5.28 | −10.67 | 8.44 | −71.02 | 0.44 | −10.20 |
4 | 1NT1 | 246 | 1.28 | −13.2 | 1.33 | −12.53 | 3.63 | −11.50 | 1.66 | −67.53 | 0.61 | −11.43 |
5 | 1PKF | 412 | 1.05 | −13.3 | 1.59 | −13.56 | 5.41 | −14.72 | 0.67 | −78.59 | 2.03 | −8.86 |
6 | 1R8Q | 109 | 0.50 | −11.5 | 1.23 | −10.43 | 5.28 | −11.92 | 0.44 | −63.66 | 0.38 | −11.66 |
7 | 1UU3 | 38 | 1.00 | −10.9 | 1.27 | −11.16 | 5.77 | −11.40 | 1.64 | −83.79 | 0.78 | −10.58 |
8 | 1W96 | 278 | 0.45 | −11.7 | 0.69 | −12.27 | 0.64 | −12.66 | 0.41 | −86.84 | 0.52 | −8.92 |
9 | 2C6H | 69 | 0.58 | −10.9 | 3.94 | −9.86 | 1.49 | −11.83 | 0.75 | −84.40 | 1.17 | −7.02 |
10 | 2E9U | 36 | 0.82 | −10.9 | 0.79 | −8.98 | 0.91 | −10.12 | 1.06 | −60.40 | 0.36 | −8.75 |
11 | 2IYA | 265 | 0.62 | −11.8 | 0.98 | −16.08 | 1.15 | −14.82 | 0.94 | −99.18 | 1.39 | −9.99 |
12 | 2VWC | 60 | 0.70 | −9.8 | 0.79 | −9.36 | 0.79 | −10.87 | 0.59 | −76.21 | 5.36 | −6.15 |
13 | 2XBK | 373 | 1.09 | −16.3 | 1.72 | −19.73 | 1.39 | −18.66 | 0.65 | −111.52 | 1.12 | −12.84 |
14 | 2XX5 | 422 | 1.14 | −11.3 | 6.41 | −11.49 | 5.47 | −9.68 | 1.24 | −73.53 | 1.15 | −8.96 |
15 | 3DV1 | 1106 | 0.90 | −11.4 | 1.14 | −13.05 | 1.29 | −13.48 | 1.03 | −96.73 | 1.14 | −10.68 |
16 | 3DV5 | 1402 | 0.92 | −12.4 | 1.10 | −14.39 | 0.76 | −16.47 | 0.56 | −102.58 | 1.94 | −8.04 |
17 | 3EKS | 17 | 0.61 | −10.8 | 0.71 | −12.97 | 0.61 | −12.37 | 0.64 | −70.42 | 0.67 | −10.02 |
18 | 3QTF | 24 | 0.94 | −13.4 | 1.28 | −11.59 | 1.75 | −13.73 | 0.59 | −74.86 | 0.94 | −11.62 |
19 | 3UYK | 78 | 2.23 | −10.0 | 4.88 | −10.57 | 5.30 | −10.78 | 2.30 | −52.57 | 2.33 | −7.46 |
20 | 4DRU | 50 | 1.50 | −13.1 | 1.31 | −12.56 | 1.82 | −12.90 | 1.64 | −77.54 | 1.44 | −8.23 |
mean | 1.31 ± 0.36 | 1.69 ± 0.34 | 2.62 ± 0.45 | 1.34 ± 0.39 | 1.29 ± 0.25 | |||||||
SD | 1.60 | 1.54 | 2.01 | 1.75 | 1.11 | |||||||
median | 0.93 | 1.19 | 1.62 | 0.81 | 1.13 | |||||||
mean corr. b | 0.90 ± 0.08 | 1.09 ± 0.07 | 0.94 ± 0.10 | 0.95 ± 0.11 |
No. of Conform. | AD Vina | PSOVina | ||||||
---|---|---|---|---|---|---|---|---|
RMSD | Score | Time | RMSD | Score | Time | |||
1 | 1ESV | 73 | 0.47 | −10.7 | 8 min | 0.47 | −10.71 | 5 min |
5 | 1PKF | 412 | 1.05 | −13.3 | 71 min | 1.04 | −13.26 | 52 min |
6 | 1R8Q | 109 | 0.50 | −11.5 | 11 min | 0.48 | −11.50 | 8 min |
8 | 1W96 | 278 | 0.45 | −11.7 | 66 min | 0.45 | −11.72 | 50 min |
9 | 2C6H | 69 | 0.58 | −10.9 | 11 min | 0.58 | −10.85 | 15 min |
11 | 2IYA | 265 | 0.62 | −11.8 | 180 min | 0.96 | −11.86 | 85 min |
13 | 2XBK | 373 | 1.09 | −16.3 | 225 min | 1.10 | −16.24 | 101 min |
19 | 3UYK | 78 | 2.23 | −10.0 | 6 min | 2.25 | −10.01 | 10 min |
mean | 0.87 ± 0.21 | 0.92 ± 0.21 | ||||||
SD | 0.60 | 0.60 | ||||||
median | 0.60 | 0.77 |
No. Conf. | AD Vina | AD 4.2 | AD 3.0 | DOCK | Glide | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
RMSD | Score | Pose a | RMSD | Score | Pose | RMSD | Score | Pose | RMSD | Score | Pose | RMSD | Score | Pose | |||
1 | 1ESV | 73 | 0.47 | −10.7 | 1 | 0.61 | −9.29 | 5 | 0.82 | −11.24 | 4 | 0.59 | −61.98 | 1 | 0.36 | −8.31 | 3 |
2 | 1FKD | 315 | 1.04 | −9.0 | 2 | 1.09 | −10.29 | 1 | 1.63 | −9.12 | 5 | 0.86 | −71.40 | 1 | 1.12 | −6.94 | 6 |
3 | 1NM6 | 531 | 0.92 | −10.8 | 3 | 0.89 | −12.17 | 1 | 2.34 | −10.10 | 3 | 2.31 | −67.63 | 7 | 0.44 | −10.20 | 1 |
4 | 1NT1 | 246 | 1.28 | −13.2 | 1 | 0.85 | −11.63 | 9 | 2.90 | −11.18 | 4 | 1.66 | −67.53 | 1 | 0.48 | −11.14 | 2 |
5 | 1PKF | 412 | 0.58 | −12.8 | 9 | 1.20 | −13.05 | 8 | 2.07 | −14.18 | 8 | 0.67 | −78.59 | 1 | 2.03 | −8.86 | 1 |
6 | 1R8Q | 109 | 0.50 | −11.5 | 1 | 0.84 | −10.31 | 3 | 0.75 | −11.52 | 7 | 0.44 | −63.66 | 1 | 0.38 | −11.66 | 1 |
7 | 1UU3 | 38 | 1.00 | −10.9 | 1 | 1.27 | −11.16 | 1 | 1.00 | −11.07 | 5 | 1.14 | −79.11 | 4 | 0.78 | −10.58 | 1 |
8 | 1W96 | 278 | 0.45 | −11.7 | 1 | 0.69 | −12.27 | 1 | 0.64 | −12.66 | 1 | 0.41 | −86.84 | 1 | 0.52 | −8.92 | 1 |
9 | 2C6H | 69 | 0.56 | −10.8 | 2 | 0.79 | −9.69 | 5 | 0.88 | −11.46 | 5 | 0.75 | −84.40 | 1 | 0.82 | −6.85 | 15 |
10 | 2E9U | 36 | 0.82 | −10.9 | 1 | 0.79 | −8.98 | 1 | 0.91 | −10.12 | 1 | 1.06 | −60.40 | 1 | 0.36 | −8.75 | 1 |
11 | 2IYA | 265 | 0.52 | −11.7 | 5 | 0.98 | −16.08 | 1 | 0.53 | −14.64 | 4 | 0.94 | −99.18 | 1 | 1.39 | −9.99 | 1 |
12 | 2VWC | 60 | 0.70 | −9.8 | 1 | 0.79 | −9.36 | 1 | 0.79 | −10.87 | 1 | 0.59 | −76.21 | 1 | 5.36 c | −6.15 | 1 |
13 | 2XBK | 373 | 0.66 | −16.2 | 3 | 1.72 | −19.73 | 1 | 1.39 | −18.66 | 1 | 0.65 | −111.52 | 1 | 0.80 | −12.74 | 4 |
14 | 2XX5 | 422 | 0.77 | −10.8 | 5 | 1.74 | −10.42 b | 43 | 4.81 | −9.59 | 8 | 1.24 | −73.53 | 1 | 0.91 | −8.91 | 4 |
15 | 3DV1 | 1106 | 0.90 | −11.4 | 1 | 0.92 | −12.80 | 6 | 1.29 | −13.48 | 1 | 0.86 | −95.70 | 8 | 1.14 | −10.68 | 1 |
16 | 3DV5 | 1402 | 0.92 | −12.4 | 1 | 0.67 | −14.14 | 8 | 0.76 | −16.47 | 1 | 0.56 | −102.58 | 1 | 1.94 | −8.04 | 1 |
17 | 3EKS | 17 | 0.61 | −10.8 | 1 | 0.71 | −12.97 | 1 | 0.61 | −12.37 | 1 | 0.45 | −69.80 | 4 | 0.31 | −10.00 | 2 |
18 | 3QTF | 24 | 0.56 | −13.3 | 2 | 0.81 | −11.14 | 9 | 1.75 | −13.73 | 1 | 0.59 | −74.86 | 1 | 0.52 | −10.97 | 3 |
19 | 3UYK | 78 | 2.23 | −10.0 | 1 | 1.56 | −9.77 | 10 | 1.57 | −10.24 | 5 | 1.57 | −49.93 | 15 | 1.69 | −7.45 | 2 |
20 | 4DRU | 50 | 1.07 | −12.9 | 5 | 1.31 | −12.56 | 1 | 1.82 | −12.90 | 1 | 1.30 | −76.28 | 3 | 1.44 | −8.23 | 1 |
mean | 0.83 ± 0.09 | 0.97 ± 0.08 | 1.46 ± 0.22 | 0.93 ± 0.11 | 0.92 ± 0.25 | ||||||||||||
SD | 0.39 | 0.34 | 0.99 | 0.48 | 0.54 | ||||||||||||
median | 0.74 | 0.87 | 1.15 | 0.81 | 0.81 |
AD 4.2 (Table 4) | AD 4.2//Vina | ||||||
---|---|---|---|---|---|---|---|
RMSD | Score | Pose | RMSD | Score | Pose | ||
1 | 1ESV | 0.61 | −9.29 | 5 | 0.47 | −8.68 | 1 |
2 | 1FKD | 1.09 | −10.29 | 1 | 1.20 | −8.79 | 1 |
3 | 1NM6 | 0.89 | −12.17 | 1 | 0.92 | −10.84 | 1 |
4 | 1NT1 | 0.85 | −11.63 | 9 | 1.28 | −12.20 | 1 |
5 | 1PKF | 1.20 | −13.05 | 8 | 1.23 | −12.66 | 1 |
6 | 1R8Q | 0.84 | −10.31 | 3 | 0.98 | −9.90 | 1 |
7 | 1UU3 | 1.27 | −11.16 | 1 | 1.00 | −11.51 | 1 |
8 | 1W96 | 0.69 | −12.27 | 1 | 0.45 | −12.07 | 1 |
9 | 2C6H | 0.79 | −9.69 | 5 | 0.58 | −10.15 | 1 |
10 | 2E9U | 0.79 | −8.98 | 1 | 0.82 | −8.70 | 1 |
11 | 2IYA | 0.98 | −16.08 | 1 | 1.23 | −14.99 | 1 |
12 | 2VWC | 0.79 | −9.36 | 1 | 0.70 | −9.27 | 1 |
13 | 2XBK | 1.72 | −19.73 | 1 | 1.19 | −17.10 | 1 |
14 | 2XX5 | 1.74 | −10.42 | 43 | 1.59 | −10.52 | 4 |
15 | 3DV1 | 0.92 | −12.80 | 6 | 0.97 | −12.45 | 1 |
16 | 3DV5 | 0.67 | −14.14 | 8 | 1.05 | −13.92 | 1 |
17 | 3EKS | 0.71 | −12.97 | 1 | 1.14 | −12.44 | 1 |
18 | 3QTF | 0.81 | −11.14 | 9 | 0.98 | −11.99 | 1 |
19 | 3UYK | 1.56 | −9.77 | 10 | 2.23 | −9.36 | 1 |
20 | 4DRU | 1.31 | −12.56 | 1 | 1.07 | −13.20 | 1 |
mean | 0.97 ± 0.08 | 1.05 ± 0.09 | |||||
SD | 0.34 | 0.39 | |||||
median | 0.87 | 1.03 |
DOCK 6.5 | |||||
Re-Scoring | Re-Scoring | ||||
RMSD | GBSA | RMSD | Amber | ||
7 | 1UU3 | 1.69 | −77.37 | 1.10 | −58.20 |
15 | 3DV1 | 1.44 | −70.39 | 1.42 | −40.49 |
19 | 3UYK | 2.30 | −43.23 | 1.39 | −41.89 |
Glide | |||||
Re-Scoring | Re-Scoring | ||||
RMSD | XP | RMSD | MM-GBSA | ||
2 | 1FKD | 1.35 | −9.15 | 1.47 | −108.69 |
9 | 2C6H | 1.11 | −7.00 | 1.49 | −113.55 |
12 | 2VWC | 0.95 | −6.80 | 0.95 | −91.98 |
13 | 2XBK | 1.04 | −14.54 | 0.83 | −153.96 |
14 | 2XX5 | 1.10 | −10.13 | 1.10 | −97.36 |
19 | 3UYK | 1.93 | −12.30 | 1.71 | −90.04 |
© 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).
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Castro-Alvarez, A.; Costa, A.M.; Vilarrasa, J. The Performance of Several Docking Programs at Reproducing Protein–Macrolide-Like Crystal Structures. Molecules 2017, 22, 136. https://doi.org/10.3390/molecules22010136
Castro-Alvarez A, Costa AM, Vilarrasa J. The Performance of Several Docking Programs at Reproducing Protein–Macrolide-Like Crystal Structures. Molecules. 2017; 22(1):136. https://doi.org/10.3390/molecules22010136
Chicago/Turabian StyleCastro-Alvarez, Alejandro, Anna M. Costa, and Jaume Vilarrasa. 2017. "The Performance of Several Docking Programs at Reproducing Protein–Macrolide-Like Crystal Structures" Molecules 22, no. 1: 136. https://doi.org/10.3390/molecules22010136