The influence of solvent representation on nuclear shielding calculations of protonation states of small biological molecules

TL;DR

This paper evaluates how different solvation models affect nuclear shielding calculations of amino acids, highlighting limitations of implicit models and proposing a hybrid approach that better matches experimental data.

Contribution

It introduces a hybrid solvation method that accounts for direct water interactions, improving nuclear shielding predictions for protonation states of biological molecules.

Findings

Implicit solvent models have significant shortcomings.

The hybrid approach improves agreement with experimental data.

Direct water interactions are crucial for accurate protonation state calculations.

Abstract

In this study, we assess the influence of solvation on the accuracy and reliability of nuclear shielding calculations for amino acids in comparison to experimental data. We focus particularly on the performance of solvation methods for different protonation states, as biological molecules occur almost exclusively in aqueous solution and are subject to protonation with pH. We identify significant shortcomings of current implicit solvent models and present a hybrid solvation approach that improves agreement with experimental data by taking into account the presence of direct interactions between amino acid protonation state and water molecules.