Exploring the impact of alignment media on RDC analysis of phosphorus-containing compounds: a molecular docking approach

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216275%3A25310%2F23%3A39921084" target="_blank" >RIV/00216275:25310/23:39921084 - isvavai.cz</a>

Alternative codes found

RIV/61388963:_____/24:00581606 RIV/00216208:11310/24:10476442 RIV/00216275:25310/24:39921084 RIV/60461373:22310/24:43929343

Result on the web

<a href="https://pubs.rsc.org/en/content/articlelanding/2024/cp/d3cp04099b" target="_blank" >https://pubs.rsc.org/en/content/articlelanding/2024/cp/d3cp04099b</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/d3cp04099b" target="_blank" >10.1039/d3cp04099b</a>

Result language

angličtina

Original language name

Exploring the impact of alignment media on RDC analysis of phosphorus-containing compounds: a molecular docking approach

Original language description

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. Two different docked poses of two diastereoisomers accommodated in the PBLG helix. Conformational change caused by PBLG was used for generation of new ensembles of conformers for RDC analysis.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10401 - Organic chemistry

Project

<a href="/en/project/GA21-23014S" target="_blank" >GA21-23014S: NMR Toolbox for Probing Stereochemistry in Phosphorus-Containing Bioactive Molecules</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Physical Chemistry Chemical Physics

ISSN

1463-9076

e-ISSN

1463-9084

Volume of the periodical

26

Issue of the periodical within the volume

3

Country of publishing house

GB - UNITED KINGDOM

Number of pages

9

Pages from-to

2016-2024

UT code for WoS article

001128318400001

EID of the result in the Scopus database

2-s2.0-85180564892