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Exploring the impact of alignment media on RDC analysis of phosphorus-containing compounds: a molecular docking approach
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SYSNO ASEP 0581606 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Exploring the impact of alignment media on RDC analysis of phosphorus-containing compounds: a molecular docking approach Author(s) Christou Tichotová, Markéta (UOCHB-X) ORCID
Tučková, Lucie (UOCHB-X) ORCID
Kocek, Hugo (UOCHB-X) ORCID
Růžička, A. (CZ)
Straka, Michal (UOCHB-X) RID, ORCID
Procházková, Eliška (UOCHB-X) RID, ORCIDSource Title Physical Chemistry Chemical Physics. - : Royal Society of Chemistry - ISSN 1463-9076
Roč. 26, č. 3 (2024), s. 2016-2024Number of pages 9 s. Language eng - English Country GB - United Kingdom Keywords residual dipolar couplings ; benzyl-L-glutamate ; NMR spectroscopy OECD category Physical chemistry R&D Projects GA21-23014S GA ČR - Czech Science Foundation (CSF) Method of publishing Open access Institutional support UOCHB-X - RVO:61388963 UT WOS 001128318400001 EID SCOPUS 85180564892 DOI 10.1039/d3cp04099b Annotation Residual dipolar couplings (RDCs) are employed in NMR analysis when conventional methods, such as J-couplings and nuclear Overhauser effects (NOEs) fail. Low-energy (optimized) conformers are often used as input structures in RDC analysis programs. However, these low-energy structures do not necessarily resemble conformations found in anisotropic environments due to interactions with the alignment medium, especially if the analyte molecules are flexible. Considering interactions with alignment media in RDC analysis, we developed and evaluated a molecular docking-based approach to generate more accurate conformer ensembles for compounds in the presence of the poly-gamma-benzyl-l-glutamate alignment medium. We designed chiral phosphorus-containing compounds that enabled us to utilize 31P NMR parameters for the stereochemical analysis. Using P3D/PALES software to evaluate diastereomer discrimination, we found that our conformer ensembles outperform moderately the standard, low-energy conformers in RDC analysis. To further improve our results, we (i) averaged the experimental values of the molecular docking-based conformers by applying the Boltzmann distribution and (ii) optimized the structures through normal mode relaxation, thereby enhancing the Pearson correlation factor R and even diastereomer discrimination in some cases. Nevertheless, we presume that significant differences between J-couplings in isotropic and in anisotropic environments may preclude RDC measurements for flexible molecules. Therefore, generating conformer ensembles based on molecular docking enhances RDC analysis for mildly flexible systems while flexible molecules may require applying more advanced approaches, in particular approaches including dynamical effects. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Year of Publishing 2025 Electronic address https://doi.org/10.1039/D3CP04099B
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