title: Absolute pKa 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.
authors.affiliation: Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge CB2 1EW, United Kingdom.
authors.forename: Martina
authors.initials: M
authors.lastname: Mangold
authors.affiliation: Departement de Chimie, Ecole Normale Superieure , 24 rue Lhomond, 75231 Paris Cedex 05, France.
authors.forename: Leslie
authors.initials: L
authors.lastname: Rolland
authors.affiliation: Dipartimento di Chimica Fisica e Inorganica, Universita di Bologna , Viale Risorgimento 4, I-40136 Bologna, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Costanzo
authors.affiliation: Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge CB2 1EW, United Kingdom.
authors.forename: Michiel
authors.initials: M
authors.lastname: Sprik
authors.affiliation: Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge CB2 1EW, United Kingdom.
authors.forename: Marialore
authors.initials: M
authors.lastname: Sulpizi
authors.affiliation: Department of Physics and Astronomy, University College London , London WC1E 6BT, United Kingdom.
authors.forename: Jochen
authors.initials: J
authors.lastname: Blumberger