On the Calculation of Puckering Free Energy Surfaces

TL;DR

This paper evaluates different Cremer-Pople puckering coordinate parametrizations and demonstrates that only the polar parametrization provides an unbiased free energy surface for cyclic compounds, using glucuronic acid as an example.

Contribution

It clarifies which puckering coordinate parametrization accurately captures the free energy landscape of cyclic molecules.

Findings

Polar parametrization yields unbiased free energy estimates.

Incorrect parametrizations introduce artefacts in the free energy surface.

Six-membered ring case study confirms the importance of proper parametrization.

Abstract

Cremer-Pople puckering coordinates appear to be the natural candidate variables to explore the conformational space of cyclic compounds, and in literature different parametrizations have been used to this end. However, while every parametrization is equivalent in identifying conformations, it is not obvious that they can also act as proper collective variables for the exploration of the puckered conformations free energy surface. It is shown that only the polar parametrization is fit to produce an unbiased estimate of the free energy landscape. As an example, the case of a six-membered ring, glucuronic acid, is presented, showing the artefacts that are generated when a wrong parametrization is used.