(Q)SAR Models of HIV-1 Protein Inhibition by Drug-Like Compounds
Abstract
:1. Introduction
2. Results
2.1. Training Sets
2.2. Classification Models
2.3. Quantitative Structure–Activity Relationships (QSAR) Models
2.4. Model Validation Using the External Test Sets
2.5. (Q)SAR Models Based on the Complete Dataset
2.6. Implementation of (Q)SAR Models in Web-Service
3. Discussion
4. Materials and Methods
4.1. Sources of Information for Preparation of the Training Sets
4.1.1. NIAID HIV/OI/TB DB Dataset
4.1.2. ChEMBL Datasets
4.1.3. Integrity Dataset
4.2. Data Curation Pipeline
4.3. Modeling Methods
- Each atom must be presented by an atom symbol from the periodic table;
- Each bond must be a covalent bond presented by single, double, or triple bond types only;
- The structure must include three or more carbon atoms;
- The structure must include only one component;
- The molecule must be uncharged;
- The absolute molecular weight of the substance must be less than 1250 Da.
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are not available from the authors. |
IN | PR | RT | |
---|---|---|---|
NIAID | 10,377/3459 | 7604/5972 | 8936/5675 |
ChEMBL | 2283/1430 | 2387/1437 | 2149/1390 |
Integrity | 563/328 | 316/268 | 731/615 |
Inhibitors of | Active | Inactive | IAP |
---|---|---|---|
HIV-1 IN | 1813/1622 | 2108/1930 | 0.924/0.922 |
HIV-1 PR | 4762/4504 | 1337/1298 | 0.938/0.937 |
HIV-1 RT | 3142/3054 | 2854/2752 | 0.878/0.878 |
Inhibitors of | N | R2 | Q2 | RMSD | V |
---|---|---|---|---|---|
IN | 3987/3597 | 0.960/0.960 | 0.821/0.819 | 0.587/0.592 | 384/371 |
PR | 6462/6068 | 0.956/0.957 | 0.829/0.827 | 0.696/0.710 | 494/485 |
RT | 6093/5894 | 0.943/0.942 | 0.723/0.715 | 0.760/0.776 | 455/441 |
Model | Test Set | Sensitivity | Specificity | Balanced Accuracy |
---|---|---|---|---|
IN, NIAID and ChEMBL | IN, Integrity test set | 0.753 | 0.677 | 0.715 |
IN, NIAID and Integrity | IN, ChEMBL test set | 0.813 | 0.820 | 0.817 |
PR, NIAID and ChEMBL | PR, Integrity test set | 0.697 | 0.857 | 0.777 |
PR, NIAID and Integrity | PR, ChEMBL test set | 0.826 | 0.788 | 0.807 |
RT, NIAID and ChEMBL | RT, Integrity test set | 0.611 | 0.620 | 0.615 |
RT, NIAID and Integrity | RT, ChEMBL test set | 0.596 | 0.867 | 0.732 |
Inhibitors of | Active | Inactive | IAP LOO CV | IAP 20-fold CV |
---|---|---|---|---|
IN | 1884 | 2139 | 0.922 | 0.921 |
PR | 4840 | 1351 | 0.937 | 0.936 |
RT | 3286 | 2935 | 0.876 | 0.875 |
Inhibitors of | N | R2 | Q2 | RMSD | V |
---|---|---|---|---|---|
IN | 4091 | 0.96 | 0.818 | 0.595 | 392 |
PR | 6554 | 0.954 | 0.824 | 0.709 | 470 |
RT | 6309 | 0.941 | 0.714 | 0.767 | 452 |
IN | PR | RT | |
---|---|---|---|
ChEMBL and NIAID | 104 | 92 | 216 |
Integrity and NIAID | 494 | 486 | 415 |
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Stolbov, L.A.; Druzhilovskiy, D.S.; Filimonov, D.A.; Nicklaus, M.C.; Poroikov, V.V. (Q)SAR Models of HIV-1 Protein Inhibition by Drug-Like Compounds. Molecules 2020, 25, 87. https://doi.org/10.3390/molecules25010087
Stolbov LA, Druzhilovskiy DS, Filimonov DA, Nicklaus MC, Poroikov VV. (Q)SAR Models of HIV-1 Protein Inhibition by Drug-Like Compounds. Molecules. 2020; 25(1):87. https://doi.org/10.3390/molecules25010087
Chicago/Turabian StyleStolbov, Leonid A., Dmitry S. Druzhilovskiy, Dmitry A. Filimonov, Marc C. Nicklaus, and Vladimir V. Poroikov. 2020. "(Q)SAR Models of HIV-1 Protein Inhibition by Drug-Like Compounds" Molecules 25, no. 1: 87. https://doi.org/10.3390/molecules25010087