title: Fast Proton Titration Scheme for Multiscale Modeling of Protein Solutions.
abstract: Proton exchange between titratable amino acid residues and the surrounding solution gives rise to exciting electric processes in proteins. We present a proton titration scheme for studying acid-base equilibria in Metropolis Monte Carlo simulations where salt is treated at the Debye-Hückel level. The method, rooted in the Kirkwood model of impenetrable spheres, is applied on the three milk proteins α-lactalbumin, β-lactoglobulin, and lactoferrin, for which we investigate the net-charge, molecular dipole moment, and charge capacitance. Over a wide range of pH and salt conditions, excellent agreement is found with more elaborate simulations where salt is explicitly included. The implicit salt scheme is orders of magnitude faster than the explicit analog and allows for transparent interpretation of physical mechanisms. It is shown how the method can be expanded to multiscale modeling of aqueous salt solutions of many biomolecules with nonstatic charge distributions. Important examples are protein-protein aggregation, protein-polyelectrolyte complexation, and protein-membrane association.
authors.affiliation: Department of Physics and Chemistry, 14040-903 Av. do café, s/no., FCFRP-USP, Ribeirão Preto, SP, Brazil, Department of Theoretical Chemistry Chemical Center, Lund University, P.O. Box 124-S-221 00, Lund, Sweden, and Department of Physics and Chemistry, 14040-903 Av. do café, s/no., FCFRP-USP, Ribeirão Preto, SP, Brazil.
authors.forename: Andre Azevedo Reis
authors.initials: AA
authors.lastname: Teixeira
authors.affiliation: Department of Physics and Chemistry, 14040-903 Av. do café, s/no., FCFRP-USP, Ribeirão Preto, SP, Brazil, Department of Theoretical Chemistry Chemical Center, Lund University, P.O. Box 124-S-221 00, Lund, Sweden, and Department of Physics and Chemistry, 14040-903 Av. do café, s/no., FCFRP-USP, Ribeirão Preto, SP, Brazil.
authors.forename: Mikael
authors.initials: M
authors.lastname: Lund
authors.affiliation: Department of Physics and Chemistry, 14040-903 Av. do café, s/no., FCFRP-USP, Ribeirão Preto, SP, Brazil, Department of Theoretical Chemistry Chemical Center, Lund University, P.O. Box 124-S-221 00, Lund, Sweden, and Department of Physics and Chemistry, 14040-903 Av. do café, s/no., FCFRP-USP, Ribeirão Preto, SP, Brazil.
authors.forename: Fernando Luís Barroso
authors.initials: FL
authors.lastname: da Silva