Puckering Free Energy of Pyranoses: an NMR and Metadynamics--Umbrella Sampling Investigation

TL;DR

This study combines metadynamics and umbrella sampling to analyze pyranose puckering free energies, revealing limitations of the gromos 45a4 force field and proposing modifications to improve accuracy, supported by NMR experimental validation.

Contribution

It introduces a modified gromos 45a4 force field that better reproduces puckering free energies of pyranoses, validated by NMR data.

Findings

Current force field poorly predicts puckering free energies.

Modified parameters significantly improve simulation accuracy.

NMR measurements align well with theoretical predictions.

Abstract

We present the results of a combined metadynamics--umbrella sampling investigation of the puckered conformers of pyranoses described using the gromos 45a4 force field. The free energy landscape of Cremer--Pople puckering coordinates has been calculated for the whole series of alpha and beta aldohexoses, showing that the current force field parameters fail in reproducing proper puckering free energy differences between chair conformers. We suggest a modification to the gromos 45a4 parameter set which improves considerably the agreement of simulation results with theoretical and experimental estimates of puckering free energies. We also report on the experimental measurement of altrose conformers populations by means of NMR spectroscopy, which show good agreement with the predictions of current theoretical models.