Charge-Neutral Constant pH Molecular Dynamics Simulations Using a Parsimonious Proton Buffer

Journal of Chemical Theory and Computation
Serena DonniniHelmut Grubmüller

Abstract

In constant pH molecular dynamics simulations, the protonation states of titratable sites can respond to changes of the pH and of their electrostatic environment. Consequently, the number of protons bound to the biomolecule, and therefore the overall charge of the system, fluctuates during the simulation. To avoid artifacts associated with a non-neutral simulation system, we introduce an approach to maintain neutrality of the simulation box in constant pH molecular dynamics simulations, while maintaining an accurate description of all protonation fluctuations. Specifically, we introduce a proton buffer that, like a buffer in experiment, can exchange protons with the biomolecule enabling its charge to fluctuate. To keep the total charge of the system constant, the uptake and release of protons by the buffer are coupled to the titration of the biomolecule with a constraint. We find that, because the fluctuation of the total charge (number of protons) of a typical biomolecule is much smaller than the number of titratable sites of the biomolecule, the number of buffer sites required to maintain overall charge neutrality without compromising the charge fluctuations of the biomolecule, is typically much smaller than the number of tit...Continue Reading

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Citations

Aug 20, 2016·Journal of Chemical Theory and Computation·Ernest Awoonor-Williams, Christopher N Rowley
Oct 7, 2016·Journal of Chemical Theory and Computation·Yandong HuangJana Shen
Apr 6, 2017·Journal of Chemical Theory and Computation·Fernando Luís Barroso da Silva, Donal MacKernan
Jan 23, 2017·The Journal of Chemical Physics·Fernando Luís Barroso da SilvaSamuela Pasquali
Jan 18, 2020·Annual Review of Food Science and Technology·Fernando Luís Barroso da SilvaErik E Santiso
Sep 19, 2017·Biophysics Reviews·Fernando Luís Barroso daSilva, Luis Gustavo Dias
Dec 25, 2016·The Journal of Chemical Physics·Arjun SharmaSteven W Rick
Jul 17, 2020·The Journal of Chemical Physics·Fabian GrünewaldSiewert J Marrink
Mar 18, 2020·The Journal of Physical Chemistry. B·Piotr BatysMaria Sammalkorpi
Nov 3, 2017·Journal of Chemical Information and Modeling·Themis Lazaridis, Gerhard Hummer
May 7, 2019·Journal of Chemical Theory and Computation·Fernando Luís Barroso da SilvaPhilippe Derreumaux
Mar 21, 2020·Journal of Chemical Theory and Computation·Plamen DobrevHelmut Grubmüller
Nov 27, 2021·Biophysical Journal·Martin J FossatRohit V Pappu

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