Towards Intelligent Drug Design System: Application of Artificial Dipeptide Receptor Library in QSAR-Oriented Studies
Abstract
:1. Introduction
2. Results and Discussion
2.1. Library of Docked Anticancer Active Triazine Derivatives
2.2. In Silico Evaluation of In Vitro Anticancer Activity Using CoMSA and SMV Approach
2.3. Probing Artificial Dipeptide Receptor Library
3. Experimental Section
3.1. CoMFA Analysis
3.2. CoMSA Analysis
3.3. PLS Analysis with Iterative Variable Elimination
- Stage 1. Standard PLS analysis with LOO-CV to assess the performance of the PLS model;
- Stage 2. Elimination of the matrix column with the lowest abs(mean(b)/std(b)) value;
- Stage 3. Standard PLS analysis of the new matrix without the column cancelled in stage 2;
- Stage 4. Recurrent repetition of stages 1–3 to maximize the LOO parameter.
3.4. PCA Analysis
3.5. Artificial Dipeptide Receptor Library Synthesis
3.6. Anticancer Compounds Docking
3.7. Binding of Anticancer Active Ligands to Molecular Receptors Pockets
3.8. Model Builder & Molecular Modelling
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Sample Availability: Samples of compounds are available from authors (experimental data—Beata Kolesinska, theoretical data—Andrzej Bak). |
Comp. | Compound Structure | IC50 [μM] | Comp. | Compound Structure | IC50 [μM] |
---|---|---|---|---|---|
1 | 12.30 | 11 | 139.78 | ||
2 | 7.40 | 12 | 46.29 | ||
3 | 49.40 | 13 | 20.44 | ||
4 | 35.11 | 14 | 169.7 | ||
5 | 135.73 | 15 | 32.14 | ||
6 | 51.39 | 16 | 43.95 | ||
7 | 85.37 | 17 | 111.81 | ||
8 | 30.02 | 18 | 30.92 | ||
9 | 29.08 | 19 | 80.83 | ||
10 | 117.61 | 20 | 33.85 |
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Bak, A.; Kozik, V.; Walczak, M.; Fraczyk, J.; Kaminski, Z.; Kolesinska, B.; Smolinski, A.; Jampilek, J. Towards Intelligent Drug Design System: Application of Artificial Dipeptide Receptor Library in QSAR-Oriented Studies. Molecules 2018, 23, 1964. https://doi.org/10.3390/molecules23081964
Bak A, Kozik V, Walczak M, Fraczyk J, Kaminski Z, Kolesinska B, Smolinski A, Jampilek J. Towards Intelligent Drug Design System: Application of Artificial Dipeptide Receptor Library in QSAR-Oriented Studies. Molecules. 2018; 23(8):1964. https://doi.org/10.3390/molecules23081964
Chicago/Turabian StyleBak, Andrzej, Violetta Kozik, Malgorzata Walczak, Justyna Fraczyk, Zbigniew Kaminski, Beata Kolesinska, Adam Smolinski, and Josef Jampilek. 2018. "Towards Intelligent Drug Design System: Application of Artificial Dipeptide Receptor Library in QSAR-Oriented Studies" Molecules 23, no. 8: 1964. https://doi.org/10.3390/molecules23081964