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Improved model of hydrated calcium ion for molecular dynamics simulations using classical biomolecular force fields
Author(s) -
Yoo Jejoong,
Wilson James,
Aksimentiev Aleksei
Publication year - 2016
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.22868
Subject(s) - molecular dynamics , chemistry , force field (fiction) , ion , potential of mean force , chemical physics , nanopore , water model , molecule , calcium , osmotic pressure , dna , electric field , computational chemistry , nanotechnology , physics , materials science , organic chemistry , quantum mechanics , biochemistry
ABSTRACT Calcium ions (Ca 2+ ) play key roles in various fundamental biological processes such as cell signaling and brain function. Molecular dynamics (MD) simulations have been used to study such interactions, however, the accuracy of the Ca 2+ models provided by the standard MD force fields has not been rigorously tested. Here, we assess the performance of the Ca 2+ models from the most popular classical force fields AMBER and CHARMM by computing the osmotic pressure of model compounds and the free energy of DNA–DNA interactions. In the simulations performed using the two standard models, Ca 2+ ions are seen to form artificial clusters with chloride, acetate, and phosphate species; the osmotic pressure of CaAc 2 and CaCl 2 solutions is a small fraction of the experimental values for both force fields. Using the standard parameterization of Ca 2+ ions in the simulations of Ca 2+ ‐mediated DNA–DNA interactions leads to qualitatively wrong outcomes: both AMBER and CHARMM simulations suggest strong inter‐DNA attraction whereas, in experiment, DNA molecules repel one another. The artificial attraction of Ca 2+ to DNA phosphate is strong enough to affect the direction of the electric field‐driven translocation of DNA through a solid‐state nanopore. To address these shortcomings of the standard Ca 2+ model, we introduce a custom model of a hydrated Ca 2+ ion and show that using our model brings the results of the above MD simulations in quantitative agreement with experiment. Our improved model of Ca 2+ can be readily applied to MD simulations of various biomolecular systems, including nucleic acids, proteins and lipid bilayer membranes. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 752–763, 2016.