Absolute pK_a Values and Solvation Structure of Amino Acids from Density Functional Based Molecular Dynamics Simulation

Abstract

Absolute pKa values of the amino acid side chains of arginine, aspartate, cysteine, histidine, and tyrosine; the C- and N-terminal group of tyrosine; and the tryptophan radical cation are calculated using a revised density functional based molecular dynamics simulation technique introduced previously [ Cheng , J. ; Sulpizi , M. ; Sprik , M. J. Chem. Phys. 2009 , 131 , 154504 ]. In the revised scheme, acid deprotonation is considered as a dissociation rather than a proton transfer reaction, and a correction term for treating the proton as a hydronium ion is suggested. The acidity constants of the amino acids are obtained from the vertical energy gaps for removal or insertion of the acidic proton and the computed solvation free energy of the proton. The unsigned mean error relative to experimental results is 2.1 pKa units with a maximum error of 4.0 pKa units. The estimated mean statistical uncertainty due to the finite length of the trajectories is ±1.1 pKa units. The solvation structures of the protonated and deprotonated amino acids are analyzed in terms of radial distribution functions, which can serve as reference data for future force field developments.

Absolute acidity of clay edge sites from ab-initio simulations

“…In order to evaluate the integral (2), the computationally more efficient end point approximation is not sufficiently accurate because of the non-linear response of the solvent and resort to the three-point formula (3) is necessary. As already commented in our recent work Sprik, 2008, 2010;Cheng et al, 2009;Cheng and Sprik, 2010;Costanzo et al, 2011;Mangold et al, 2011;Gaigeot et al, 2012;Sulpizi et al, 2012) the deprotonation event involves a highly non-linear response of the solvent reorganization. An easy to monitor indicator of deviations from linearity is the dependence of the variance of the energy gap fluctuations on protonation state.…”

“…The acidity constants of the different reactive groups present on the clay edge are computed using the reversible proton insertion/deletion method Sprik, 2008, 2010;Cheng et al, 2009;Costanzo et al, 2011;Mangold et al, 2011). pK a 's are estimated from the reaction free energies for the transfer of a proton from the surface to a water molecule in the bulk part of the sample.…”

“…DFT-based ab-initio simulations can also be combined with thermodynamic integration to determine the free energy of proton transfer from a given site to a water molecule, which provides a direct measure of the acidity of this site. This strategy has been successfully employed to calculate the pK a of simple aqueous compounds Sprik, 2008, 2010;Cheng et al, 2009;Costanzo et al, 2011;Mangold et al, 2011) as well as the surface acidity and point of zero charge of simple oxides in contact with water, namely titania (Cheng and Sprik, 2010), quartz and alumina . In the present work, we apply this strategy to provide the first direct calculation of the pK a of the different groups which are present on the (0 1 0) face of pyrophyllite.…”

Ab initio molecular dynamics simulation and free energy exploration of copper(I) complexation by chloride and bisulfide in hydrothermal fluids

“…This contribution is much smaller than the error obtained by experiments or MD thermodynamic integration, so the Gibbs free energies of the reaction were approximated by the Helmholtz free energy, i.e., ∆ r G = ∆A a b . This approximation has been adopted before by a number of authors (e.g., Habershon and Manolopoulos, 2011;Bühl et al, 2006;2008;Mangold et al, 2011).…”

TD-DFT study of the for coumarins

“…The majority of previous theorical works used the thermodynamic cycle to obtain the pK a [13][14][15][16][17][18][19][20] and only a few works have been dedicated to the pK Ã a [21][22][23][24][25][26][27]. Particularly for coumarins (Figure 2), which are the focus of the present paper, experimental data are rather incomplete and we are aware of only one previous ab initio study [21], performed for the same set of molecules.…”