Identification of Electronic and Structural Descriptors of Adenosine Analogues Related to Inhibition of Leishmanial Glyceraldehyde-3-Phosphate Dehydrogenase
Abstract
:1. Introduction
2. Results and Discussion
2.1. Statistical Results
Descriptor | Type | Definition |
---|---|---|
Volume | Geometric | Solvent-accessible surface-bounded molecular volume |
EHOMO | Electronic | Energy of the highest occupied molecular orbital |
HATS4e | GETAWAY | Leverage-weighted autocorrelation of lag 4/weighted by atomic Sanderson electronegativities |
HATS3u | GETAWAY | Leverage-weighted autocorrelation of lag 3/unweighted |
H7m | GETAWAY | H autocorrelation of lag 2/weighted by atomic masses |
Mor23v | 3D-MoRSE | 3D-MoRSE-signal 23/weighted by atomic van der Waals volumes |
BELp1 | BCUT | Lowest eigenvalue n.1 of Burden matrix/weighted by atomic polarizabilities |
JGI2 | Galvez topological charge indices | Mean topological charge index of order 2 |
E1v | WHIM | 1st component accessibility directional WHIM index, weighted by atomic van der Waals volumes |
PLS models | PCR models | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Factors | SEV | PRESS | r2 | * | PCs | SEV | PRESS | r2 | * | ||
2 | 0.401 | 7.571 | 0.885 | 0.843 | 2 | 0.388 | 7.092 | 0.873 | 0.852 | 0.854 | |
3 | 0.409 | 7.877 | 0.891 | 0.837 | 3 | 0.396 | 7.364 | 0.873 | 0.847 | ||
4 | 0.402 | 7.580 | 0.897 | 0.843 | 4 | 0.407 | 7.804 | 0.877 | 0.838 | ||
5 | 0.402 | 7.599 | 0.899 | 0.843 | 5 | 0.402 | 7.602 | 0.883 | 0.842 | ||
6 | 0.398 | 7.450 | 0.899 | 0.845 | 6 | 0.409 | 7.881 | 0.883 | 0.837 | ||
7 | 0.398 | 7.431 | 0.899 | 0.846 | 7 | 0.418 | 8.231 | 0.884 | 0.829 | ||
8 | 0.397 | 7.421 | 0.899 | 0.846 | 8 | 0.443 | 9.234 | 0.884 | 0.810 | ||
9 | 0.397 | 7.416 | 0.899 | 0.846 | 9 | 0.397 | 7.416 | 0.899 | 0.846 | ||
MLR model | |||||||||||
r2 | 0.899 | 0.845 | * | 0.842 | RMSE | 0.397 |
2.2. External Model Validation and Y-Randomization Tests
Model | SEP | * | * | |
---|---|---|---|---|
PLS | 0.900 | 0.317 | 0.097 | 0.155 |
PCR | 0.904 | 0.312 | 0.143 | 0.055 |
MLR | 0.875 | 0.346 | 0.236 | 0.248 |
Training set | Test set | ||||||
---|---|---|---|---|---|---|---|
Ranking results | p% | Ranking results | p% | ||||
Name | SRD | x < SRD > = x | Name | SRD | x < SRD > =x | ||
V1 * | 92 | 1.05 10−18 | 1.48 10−18 | V2 | 6 | 1.19 10−5 | 3.08 10−5 |
V2 | 94 | 1.48 10−18 | 1.91 10−18 | V4 | 6 | 1.19 10−5 | 3.08 10−5 |
V3 | 108 | 9.18 10−18 | 1.10 10−17 | V1 | 8 | 3.08 10−5 | 7.45 10−5 |
V4 | 140 | 5.75 10−16 | 7.00 10−16 | V3 | 12 | 1.73 10−4 | 3.88 10−4 |
XX1 | 618 | 4.80 | 5.06 | XX1 | 46 | 4.61 | 5.47 |
Q1 | 684 | 24.67 | 25.64 | Q1 | 58 | 24.45 | 27.12 |
Med | 732 | 49.24 | 50.40 | Med | 66 | 48.78 | 52.08 |
Q3 | 778 | 74.96 | 75.88 | Q3 | 74 | 73.59 | 76.22 |
XX19 | 846 | 94.79 | 95.10 | XX19 | 84 | 94.77 | 95.59 |
2.3. Applicability Domain
2.4. Molecular Implications for Ligand Design
3. Experimental
3.1. Data Sets
Training set compounds | |||||
---|---|---|---|---|---|
Cpd | Structure | pIC50 | Cpd | Structure | pIC50 |
1 | 3.30 | 2 | 2.40 | ||
3 | 3.60 | 4 | 3.12 | ||
5 | 2.62 | 6 | 3.40 | ||
7 | 3.30 | 8 | 3.15 | ||
9 | 3.52 | 10 | 3.15 | ||
11 | 2.22 | 12 | 2.74 | ||
13 | 2.40 | 14 | 3.60 | ||
15 | 2.48 | 16 | 3.40 | ||
17 | 3.30 | 18 | 2.52 | ||
19 | 4.70 | 20 | 4.60 | ||
21 | 4.60 | 22 | 4.60 | ||
23 | 4.60 | 24 | 5.26 | ||
25 | 4.10 | 26 | 5.00 | ||
27 | 5.70 | 28 | 4.92 | ||
29 | 5.00 | 30 | 5.30 | ||
31 | 4.30 | 32 | 4.60 | ||
33 | 4.00 | 34 | 4.10 | ||
35 | 5.00 | 36 | 4.60 | ||
37 | 5.70 | 38 | 4.60 | ||
39 | 4.60 | 40 | 4.00 | ||
41 | 5.70 | 42 | 5.22 | ||
43 | 5.40 | 44 | 4.60 | ||
45 | 5.30 | 46 | 5.70 | ||
47 | 4.60 | 48 | 2.80 | ||
49 | 3.15 | 50 | 3.44 | ||
51 | 3.82 | 52 | 2.52 | ||
53 | 3.70 | 54 | 3.22 | ||
55 | 5.30 | 56 | 4.22 | ||
57 | 5.40 | 58 | 4.43 | ||
59 | 5.70 | 60 | 4.74 | ||
61 | 5.00 |
3.2. Descriptor Calculation and Selection
4. Conclusions
Supplementary Materials
Acknowledgments
References
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Lozano, N.B.H.; Oliveira, R.F.; Weber, K.C.; Honorio, K.M.; Guido, R.V.; Andricopulo, A.D.; Silva, A.B.F.D. Identification of Electronic and Structural Descriptors of Adenosine Analogues Related to Inhibition of Leishmanial Glyceraldehyde-3-Phosphate Dehydrogenase. Molecules 2013, 18, 5032-5050. https://doi.org/10.3390/molecules18055032
Lozano NBH, Oliveira RF, Weber KC, Honorio KM, Guido RV, Andricopulo AD, Silva ABFD. Identification of Electronic and Structural Descriptors of Adenosine Analogues Related to Inhibition of Leishmanial Glyceraldehyde-3-Phosphate Dehydrogenase. Molecules. 2013; 18(5):5032-5050. https://doi.org/10.3390/molecules18055032
Chicago/Turabian StyleLozano, Norka B. H., Rafael F. Oliveira, Karen C. Weber, Kathia M. Honorio, Rafael V. Guido, Adriano D. Andricopulo, and Albérico B. F. Da Silva. 2013. "Identification of Electronic and Structural Descriptors of Adenosine Analogues Related to Inhibition of Leishmanial Glyceraldehyde-3-Phosphate Dehydrogenase" Molecules 18, no. 5: 5032-5050. https://doi.org/10.3390/molecules18055032