Incomplete Data Sets in the Model Free Analysis of Experimental Residual Dipolar Couplings in Small Organic Compounds

10.26434/chemrxiv.14636316 ◽

2021 ◽

Author(s):

Felix Roth ◽

Volker Schmidts ◽

Jan Rettig ◽

Christina Thiele

Keyword(s):

Organic Compounds ◽

Residual Dipolar Couplings ◽

De Novo ◽

Structure Refinement ◽

Dipolar Couplings ◽

Data Sets ◽

Relative Configuration ◽

Structure And Dynamics ◽

Model Free ◽

Relative Arrangement

Residual dipolar couplings (RDCs) contain information on the relative arrangement and dynamics of internuclear spin vectors in chemical compounds. The recently introduced software TITANIA implements the MFA and extracts structure and dynamics parameters directly from experimental RDCs to facilitate de novo structure refinement for small organic compounds. Herein, we focus on the challenges faced with experimentally inaccessible data often encountered for small organic compounds leading to voids in the RDC matrix and the concomitant effects on the structure refinement. It is shown that RDC data sets obtained experimentally from currently available alignment media and measurement methods are of sufficient quality to allow relative configuration determination even when the relative configuration of the analyte is completely unknown.

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Model Free Analysis of Experimental Residual Dipolar Couplings in Small Organic Compounds

Physical Chemistry Chemical Physics ◽

10.1039/d1cp02324a ◽

2021 ◽

Author(s):

Felix A Roth ◽

Volker Schmidts ◽

Jan Rettig ◽

Christina M. Thiele

Keyword(s):

Organic Compounds ◽

Residual Dipolar Couplings ◽

Chemical Compounds ◽

Dipolar Couplings ◽

Model Free ◽

Relative Arrangement

Residual dipolar couplings (RDCs) contain information on the relative arrangement and dynamics of internuclear spin vectors in chemical compounds. Classically, RDC data is analyzed by fitting to structure models, while...

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TITANIA: Model Free Interpretation of Residual Dipolar Couplings in the context of Organic Compounds

10.26434/chemrxiv.14636070 ◽

2021 ◽

Author(s):

Felix Roth ◽

Volker Schmidts ◽

Christina Thiele

Keyword(s):

Organic Compounds ◽

Iterative Procedure ◽

Residual Dipolar Couplings ◽

Multiple Alignment ◽

Dipolar Couplings ◽

Data Sets ◽

Joint Determination ◽

Model Free ◽

Direct Use

The direct use of RDCs as restraint to construct structures based on RDCs is proposed for organic compounds. It uses the vector and dynamics information available in multi alignment data sets directly for the joint determination of conformation and configuration of organic compounds. We show that employing these data even a flat or random start structure converges into the correctly configured structure when employing multiple alignment data sets in our iterative procedure.

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TITANIA: Model Free Interpretation of Residual Dipolar Couplings in the context of Organic Compounds

10.26434/chemrxiv.14636070.v1 ◽

2021 ◽

Author(s):

Felix Roth ◽

Volker Schmidts ◽

Christina Thiele

Keyword(s):

Organic Compounds ◽

Iterative Procedure ◽

Residual Dipolar Couplings ◽

Multiple Alignment ◽

Dipolar Couplings ◽

Data Sets ◽

Joint Determination ◽

Model Free ◽

Direct Use

The direct use of RDCs as restraint to construct structures based on RDCs is proposed for organic compounds. It uses the vector and dynamics information available in multi alignment data sets directly for the joint determination of conformation and configuration of organic compounds. We show that employing these data even a flat or random start structure converges into the correctly configured structure when employing multiple alignment data sets in our iterative procedure.

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Determination of the Relative Configuration of β-Amino Acid Esters Based on Residual Dipolar Couplings

European Journal of Organic Chemistry ◽

10.1002/ejoc.201500941 ◽

2015 ◽

Vol 2015 (31) ◽

pp. 6801-6805 ◽

Cited By ~ 3

Author(s):

Thomas Niklas ◽

Christian Steinmetzger ◽

Weiping Liu ◽

Daniel Zell ◽

Dietmar Stalke ◽

...

Keyword(s):

Amino Acid ◽

Residual Dipolar Couplings ◽

Dipolar Couplings ◽

Amino Acid Esters ◽

Relative Configuration ◽

Acid Esters

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Improvements to REDCRAFT: a software tool for simultaneous characterization of protein backbone structure and dynamics from residual dipolar couplings

Journal of Biomolecular NMR ◽

10.1007/s10858-014-9871-x ◽

2014 ◽

Vol 60 (4) ◽

pp. 241-264 ◽

Cited By ~ 6

Author(s):

Mikhail Simin ◽

Stephanie Irausquin ◽

Casey A. Cole ◽

Homayoun Valafar

Keyword(s):

Residual Dipolar Couplings ◽

Software Tool ◽

Dipolar Couplings ◽

Protein Backbone ◽

Structure And Dynamics ◽

Backbone Structure

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Faculty Opinions recommendation of De novo determination of protein backbone structure from residual dipolar couplings using Rosetta.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1006182.77113 ◽

2002 ◽

Author(s):

Kristina Downing

Keyword(s):

Residual Dipolar Couplings ◽

De Novo ◽

Dipolar Couplings ◽

Protein Backbone ◽

Backbone Structure

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Relative configuration of micrograms of natural compounds using proton residual chemical shift anisotropy

Nature Communications ◽

10.1038/s41467-020-18093-5 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 1

Author(s):

Nilamoni Nath ◽

Juan Carlos Fuentes-Monteverde ◽

Dawrin Pech-Puch ◽

Jaime Rodríguez ◽

Carlos Jiménez ◽

...

Keyword(s):

Chemical Shift ◽

Residual Dipolar Couplings ◽

Chemical Shift Anisotropy ◽

Dipolar Couplings ◽

Structural Determination ◽

Proton Proton ◽

Relative Configuration ◽

Similar Information ◽

3D Molecular Structure

Abstract 3D molecular structure determination is a challenge for organic compounds or natural products available in minute amounts. Proton/proton and proton/carbon correlations yield the constitution. J couplings and NOEs oftentimes supported by one-bond 1H,13C residual dipolar couplings (RDCs) or by 13C residual chemical shift anisotropies (RCSAs) provide the relative configuration. However, these RDCs or carbon RCSAs rely on 1% natural abundance of 13C preventing their use for compounds available only in quantities of a few 10’s of µgs. By contrast, 1H RCSAs provide similar information on spatial orientation of structural moieties within a molecule, while using the abundant 1H spin. Herein, 1H RCSAs are accurately measured using constrained aligning gels or liquid crystals and applied to the 3D structural determination of molecules with varying complexities. Even more, deuterated alignment media allow the elucidation of the relative configuration of around 35 µg of a briarane compound isolated from Briareum asbestinum.

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