Ab Initio Molecular Dynamics Simulations of Amino Acids in Aqueous Solutions: Estimating pKa Values from Metadynamics Sampling

The Journal of Physical Chemistry. B
Anil Kumar Tummanapelli, Sukumaran Vasudevan

Abstract

Changes in the protonation and deprotonation of amino acid residues in proteins play a key role in many biological processes and pathways. Here, we report calculations of the free-energy profile for the protonation-deprotonation reaction of the 20 canonical α amino acids in aqueous solutions using ab initio Car-Parrinello molecular dynamics simulations coupled with metadynamics sampling. We show here that the calculated change in free energy of the dissociation reaction provides estimates of the multiple pKa values of the amino acids that are in good agreement with experiment. We use the bond-length-dependent number of the protons coordinated to the hydroxyl oxygen of the carboxylic and the amine groups as the collective variables to explore the free-energy profiles of the Bronsted acid-base chemistry of amino acids in aqueous solutions. We ensure that the amino acid undergoing dissociation is solvated by at least three hydrations shells with all water molecules included in the simulations. The method works equally well for amino acids with neutral, acidic and basic side chains and provides estimates of the multiple pKa values with a mean relative error, with respect to experimental results, of 0.2 pKa units.

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Citations

Nov 10, 2015·The Journal of Physical Chemistry. B·Anil Kumar Tummanapelli, Sukumaran Vasudevan
Oct 1, 2016·The Journal of Physical Chemistry. a·Arnaldo F SilvaRoy E Bruns
Feb 9, 2017·Physical Chemistry Chemical Physics : PCCP·Kei HashimotoMitsuhiro Shibayama
May 19, 2017·Chemical Reviews·Xin YangDavid A Winkler
Dec 28, 2018·Angewandte Chemie·Jan BlasiusBarbara Kirchner
Apr 18, 2019·Physical Chemistry Chemical Physics : PCCP·Vaishali ArunachalamSukumaran Vasudevan
Sep 19, 2017·Biophysics Reviews·Fernando Luís Barroso daSilva, Luis Gustavo Dias
May 13, 2021·Chemical Reviews·Ricardo M BorgesRyan S Renslow
Oct 22, 2019·Journal of the American Chemical Society·Rafał RoszakBartosz A Grzybowski
Dec 6, 2017·Journal of Chemical Theory and Computation·Aditya Wibawa SaktiHiromi Nakai
May 20, 2020·The Journal of Physical Chemistry. B·Laura Zanetti-PolziAndrea Amadei
Feb 25, 2020·Journal of the American Chemical Society·Chongqin ZhuIvan Gladich
May 7, 2019·Journal of Chemical Theory and Computation·Fernando Luís Barroso da SilvaPhilippe Derreumaux

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