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Progressive Stereo Locking (PSL): A Residual Dipolar Coupling Based Force Field Method for Determining the Relative Configuration of Natural Products and Other Small Molecules.

Abstract：

:Establishing the relative configuration of a bioactive natural product represents the most challenging part in determining its structure. Residual dipolar couplings (RDCs) are sensitive probes of the relative spatial orientation of internuclear vectors. We adapted a force field structure calculation methodology to allow free sampling of both R and S configurations of the stereocenters of interest. The algorithm uses a floating alignment tensor in a simulated annealing protocol to identify the conformations and configurations that best fit experimental RDC and distance restraints (from NOE and J-coupling data). A unique configuration (for rigid molecules) or a very small number of configurations (for less rigid molecules) of the structural models having the lowest chiral angle energies and reasonable magnitudes of the alignment tensor are provided as the best predictions of the unknown configuration. For highly flexible molecules, the progressive locking of their stereocenters into their statistically dominant R or S state dramatically reduces the number of possible relative configurations. The result is verified by checking that the same configuration is obtained by initiating the locking from different regions of the molecule. For all molecules tested having known configurations (with conformations ranging from mostly rigid to highly flexible), the method accurately determined the correct configuration.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Cornilescu G,Ramos Alvarenga RF,Wyche TP,Bugni TS,Gil RR,Cornilescu CC,Westler WM,Markley JL,Schwieters CD

doi

10.1021/acschembio.7b00281

subject

Has Abstract

pub_date

2017-08-18 00:00:00

pages

2157-2163

issue

8

eissn

1554-8929

issn

1554-8937

journal_volume

12

pub_type

杂志文章

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