TIP5P-Consistent Treatment of Electrostatics for Biomolecular Simulations

Abstract

The inclusion of zero-mass point charges around electronegative atoms, such as oxygen, within molecular mechanical force fields is known to improve hydrogen-bonding directionality. In parallel, inclusion of lone-pairs (LPs) in the TIP5P water model increased its ability to reproduce both gas-phase and condensed-phase properties over its non-LP predecessor, TIP3P. Currently, most biomolecular parameter sets compute partial atomic charges via fitting of the classical molecular electrostatic potential (MEP) to the quantum mechanical MEP. Application of this methodology to optimize lone-pair description is therefore consistent with the current approach to modeling electrostatics and is straightforward to implement. Here, we present an atom-type specific lone-pair model, which leads to the most optimal LP placement for each atom type, and, notably, results in reproduction of the lone-pair description present in TIP5P. Carbohydrates are rich in hydroxyl groups, and development of a lone-pair inclusive carbohydrate force field for use with a lone-pair containing water model, such as TIP5P, ensures the compatibility between these two models. Implementation of this lone-pair model improves the geometry and energetics for a series of hydrogen-bonded clusters and the properties of several small molecule crystals over the non-LP containing force field.

Unraveling Cellulose Microfibrils: A Twisted Tale

“…As the use of an explicit solvent model employing lone pairs on oxygen atoms produced a noticeable effect on the magnitude of < θ Twist >, additional simulations were performed with the GLYCAM06EP carbohydrate force field, which includes lone pairs on carbohydrate oxygen atoms. While the magnitude of < θ Twist > was markedly reduced with GLYCAM06EP relative to GLYCAM06 in TIP3P solvent, this value was substantially reduced when GLYCAM06EP was combined with TIP5P solvent (Figure ).…”

Molecular simulations of carbohydrates and protein–carbohydrate interactions: motivation, issues and prospects

“…Maximal benefit from the use of improved water models, however, will probably also depend on the development of carbohydrate force fields, tuned for use with the particular water model. For example, in the case of the GLYCAM for field, consistency with the TIP5P water model was achieved by introducing lone pairs into the oxygen atoms [69]. …”

“…Each of these protocols results in a unique parameter set, with characteristic strengths and weaknesses not only in terms of performance but also in terms of ease of implementation, transferability or generality for extension to glycans outside of the original parameterization scheme or to glycomimetics, as well as compatibility with other biomolecules and solvent models [29,69]. The pie chart in Fig.…”

Carbohydrate force fields

“…The following discussion refers frequently to information contained in Tables 1 and 2. These tables contain an annotated bibliography of as many CarbFFs14–92 as the authors were able to find using a comprehensive literature search. If any have been omitted, the omission was accidental with the exception that the tables are limited to all‐atom and united‐atom classical FFs intended for molecular mechanics (MM) and MD.…”