Transferable Interactions of Li+ and Mg2+ Ions in Polarizable Models
Document Type
Article
Publication Date
2020
Digital Object Identifier (DOI)
https://doi.org/10.1063/5.0022060
Abstract
Therapeutic implications of Li+, in many cases, stem from its ability to inhibit certain Mg2+-dependent enzymes, where it interacts with or substitutes for Mg2+. The underlying details of its action are, however, unknown. Molecular simulations can provide insights, but their reliability depends on how well they describe relative interactions of Li+ and Mg2+ with water and other biochemical groups. Here, we explore, benchmark, and recommend improvements to two simulation approaches: the one that employs an all-atom polarizable molecular mechanics (MM) model and the other that uses a hybrid quantum and MM implementation of the quasi-chemical theory (QCT). The strength of the former is that it describes thermal motions explicitly and that of the latter is that it derives local contributions from electron densities. Reference data are taken from the experiment, and also obtained systematically from CCSD(T) theory, followed by a benchmarked vdW-inclusive density functional theory. We find that the QCT model predicts relative hydration energies and structures in agreement with the experiment and without the need for additional parameterization. This implies that accurate descriptions of local interactions are essential. Consistent with this observation, recalibration of local interactions in the MM model, which reduces errors from 10.0 kcal/mol to 1.4 kcal/mol, also fixes aqueous phase properties. Finally, we show that ion–ligand transferability errors in the MM model can be reduced significantly from 10.3 kcal/mol to 1.2 kcal/mol by correcting the ligand’s polarization term and by introducing Lennard-Jones cross-terms. In general, this work sets up systematic approaches to evaluate and improve molecular models of ions binding to proteins.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
The Journal of Chemical Physics, v. 153, issue 10, art. 104113
Scholar Commons Citation
Wineman-Fisher, Vered; Delgado, Julián Meléndez; Nagy, Péter R.; Jakobsson, Eric; Pandit, Sagar A.; and Varma, Sameer, "Transferable Interactions of Li+ and Mg2+ Ions in Polarizable Models" (2020). Molecular Biosciences Faculty Publications. 94.
https://digitalcommons.usf.edu/bcm_facpub/94
