Configurational Analysis by Residual Dipolar Coupling Driven Floating Chirality Distance Geometry Calculations

Area of Science:

• Computational chemistry
• Structural biology
• Organic chemistry

Background:

• Determining the configuration of chiral compounds is crucial in chemistry and drug discovery.
• Traditional methods for configurational assignment can be labor-intensive and require extensive manual evaluation.
• Residual dipolar couplings (RDCs) offer valuable structural information but integrating them into distance geometry (DG) calculations has been challenging.

Purpose of the Study:

• To develop and validate a novel computational method for the configurational assignment of chiral compounds.
• To integrate residual dipolar couplings (RDCs) into distance geometry (DG) calculations for enhanced structural determination.
• To streamline the process of determining both configuration and conformation using only observable data.

Main Methods:

• Development of a new computational program, ConArch+
• Implementation of floating chirality (fc) within 4D- and 3D-distance bounds driven dynamics (DDD) calculations.
• Integration of structural information from residual dipolar couplings (RDCs) into the DG framework.

Main Results:

• Successful demonstration of RDCs in DG calculations for configurational assignment of chiral compounds.
• Generation of relative configurations solely based on observable data (NOEs, RDCs).
• Simultaneous determination of configuration and conformation for natural products and a carbohydrate derivative.

Conclusions:

• The novel ConArch+ method effectively integrates RDCs into DG calculations, simplifying chiral compound analysis.
• This approach obviates the need for tedious manual evaluation of calculated structures against RDCs.
• The method shows significant potential for accurate and efficient determination of molecular configuration and conformation.