The acidostat method previously developed for performing explicit-solvent molecular dynamics simulations at constant pH (J. Chem. Phys. 2001, 114, 9706) is applied to polyfunctional compounds, namely 1,4-diaminobutane and a decalysine peptide. The titration behavior of 1,4-diaminobutane is investigated by performing a series of simulations at different pH, using the acidostat method. The method accounts at least to some extent for site-site coupling and reproduces the experimental pK(a) values of the compound within half a pK unit, although the simulations reveal insufficient sampling of the protonation- state variables. In a second step, the ability of the acidostat method to account for correlations between the solution pH and the structure and dynamics of a biomolecule is tested by studying the pH-dependent stability of an a.-helical decalysine peptide. To this end, four 32-ns constant-pH simulations at different pH values are performed. The results are compared to those of standard molecular dynamics simulations of a fully protonated or a fully deprotonated peptide, and to experimental data on (comparatively longer) polylysine peptides. In agreement with experiment, the peptide predominantly remains in an a.-helical conformation under high-pH conditions, but becomes disordered under low-pH conditions. The helix-coil transition pH for the peptide is found to be between 9.5 and 10.3, in good agreement with the experimental value for polylysine (10.3). The constant-pH simulations also evidence a correlation between the protonation of specific lysine side chains and the local loss of backbone hydrogen bonds and partial peptide unfolding, both effects occurring predominantly in the C-terminal region of the peptide.