Clustering of atoms relative to vector space in the Z-matrix coordinate system and 'graphical fingerprint' analysis of 3D pharmacophore structure.

Autor: Kızılcan DŞ; Department of Chemistry, Faculty of Science, Erciyes University, Kayseri, Turkey., Güzel Y; Department of Chemistry, Faculty of Science, Erciyes University, Kayseri, Turkey., Türkmenoğlu B; Department of Analytical Chemistry, Faculty of Pharmacy, Erzincan Binali Yıldırım University, Erzincan, Turkey. burcin.turkmenoglu@erzincan.edu.tr.
Jazyk: angličtina
Zdroj: Molecular diversity [Mol Divers] 2024 Dec; Vol. 28 (6), pp. 4087-4104. Date of Electronic Publication: 2024 Jan 28.
DOI: 10.1007/s11030-023-10798-1
Abstrakt: The behavior of a molecule within its environment is governed by chemical fields present in 3D space. However, beyond local descriptors in 3D, the conformations a molecule assumes, and the resulting clusters also play a role in influencing structure-activity models. This study focuses on the clustering of atoms according to the vector space of four atoms aligned in the Z-Matrix Reference system for molecular similarity. Using 3D-QSAR analysis, it was aimed to determine the pharmacophore groups as interaction points in the binding region of the β2-adrenoceptor target of fenoterol stereoisomers. Different types of local reactive descriptors of ligands have been used to elucidate points of interaction with the target. Activity values for ligand-receptor interaction energy were determined using the Levenberg-Marquardt algorithm. Using the Molecular Comparative Electron Topology method, the 3D pharmacophore model (3D-PhaM) was obtained after aligning and superimposing the molecules and was further validated by the molecular docking method. Best guesses were calculated with a non-output validation (LOO-CV) method. Finally, the data were calculated using the 'graphic fingerprint' technique. Based on the eLKlopman (Electrostatic LUMO Klopman) descriptor, the Q 2 value of this derivative set was calculated as 0.981 and the R 2 ext value is calculated as 0.998.
Competing Interests: Declarations. Competing interests: The authors declare no competing interest. Ethical approval: Not applicable. Informed consent: Not applicable. Consent for publication: All the authors as listed have consented to the manuscript’s publication.
(© 2024. The Author(s).)
Databáze: MEDLINE
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