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Molecules 2018, 23(8), 1964; https://doi.org/10.3390/molecules23081964

Towards Intelligent Drug Design System: Application of Artificial Dipeptide Receptor Library in QSAR-Oriented Studies

1
Department of Synthesis Chemistry, Faculty of Mathematics, Physics and Chemistry, University of Silesia, Szkolna 9, 40007 Katowice, Poland
2
Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90924 Lodz, Poland
3
Central Mining Institute, Gwarkow 1, 40166 Katowice, Poland
4
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojarov 10, 83232 Bratislava, Slovakia
*
Authors to whom correspondence should be addressed.
Received: 12 July 2018 / Revised: 29 July 2018 / Accepted: 5 August 2018 / Published: 6 August 2018
(This article belongs to the Section Medicinal Chemistry)
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Abstract

The pharmacophore properties of a new series of potential purinoreceptor (P2X) inhibitors determined using a coupled neural network and the partial least squares method with iterative variable elimination (IVE-PLS) are presented in a ligand-based comparative study of the molecular surface by comparative molecular surface analysis (CoMSA). Moreover, we focused on the interpretation of noticeable variations in the potential selectiveness of interactions of individual inhibitor-receptors due to their physicochemical properties; therefore, the library of artificial dipeptide receptors (ADP) was designed and examined. The resulting library response to individual inhibitors was arranged in the array, preprocessed and transformed by the principal component analysis (PCA) and PLS procedures. A dominant absolute contribution to PC1 of the Glu attached to heptanoic gating acid and Phe bonded to the linker m-phenylenediamine/triazine scaffold was revealed by the PCA. The IVE-PLS procedure indicated the receptor systems with predominant Pro bonded to the linker and Glu, Gln, Cys and Val directly attached to the gating acid. The proposed comprehensive ligand-based and simplified structure-based methodology allows the in-depth study of the performance of peptide receptors against the tested set of compounds. View Full-Text
Keywords: artificial dipeptide library; PX2 inhibitors; IVE-PLS; CoMSA; stochastic model validation artificial dipeptide library; PX2 inhibitors; IVE-PLS; CoMSA; stochastic model validation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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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.

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