Fast calculation of hydrogen-bond strengths and free energy of hydration of small molecules

For this month’s computational chemistry paper of the month, we have chosen to highlight Jazzy, a python package to calculate the strengths of hydrogen-bonds. As we all know the importance of hydrogen bond donors and acceptors in the drug discovery process.

Within this paper, Ghiandoni and Caldeweyher have taken inspiration from Gerber’s methodology to reimplement and open-source the calculation of hydrogen-bond strength and free energy of hydration of molecules. They explain the three different stages of implementation, parameter fitting and validation of their tool, Jazzy. Jazzy allows the hydrogen-bond strengths to be found on both the atomic and molecular levels, rapidly. From the studies shown within the paper, it takes just over 0.05 seconds per molecule to calculate, which is pretty impressive, with a rough idea of the hydrogen-bond strengths. Unfortunately, Jazzy’s simplicity means that it does not take into account solvents, intramolecular and supramolecular effects.

Ghiandoni et al. provide in depth explanations of the calculations within the Jazzy tool and how this method has been simplified from Gerber’s work, along with justification for all decisions. Validation took place across three different experiments. The first to examine the difference between experimental and predicted free energy, the second to examine the hydrogen-bond donor strengths (6 CDK2 inhibitors) and the final one to investigate the acceptor strengths (11 β-HSD1 inhibitors). Jazzy was very slightly outperformed by the Gerber methodology due to the removal of higher-order charge effects from the equation. Therefore, the simpler, quicker model with less computational cost getting a nearly comparable result is a huge win. When applying Jazzy in the hydrogen-bond strength tests it provided good indications of correlations and understand molecules SARs relationships.

Jazzy is an interesting tool that can allows you to calculate strength of a hydrogen donor and acceptor of atoms within and molecule and visualise these in real time, which is a huge benefit even if they are not entirely 100% accurate.

Fast calculation of hydrogen-bond strengths and free energy of hydration of small molecules.

Ghiandoni, G.M., Caldeweyher, E.  Sci Rep 13, 4143 (2023).