The generalized Barn (GB) approximation is a reasonable electrostatic model that is fast enough for use with extensive conformational sampling. This study combines the GB model with a torsion-space sampling method to compute pK(a) shifts for a series of dicarboxylic acids and amino acids, and for the active-site aspartyl dyad in HIV-1 protease. The calculations agree rather well with experiment for the small molecules Conformational analysis shows salt-bridging for the zwitterionic amino acids but otherwise modest electrostatic effects upon mean chain lengths. The calculations also show that through-space electrical fields alone cannot account completely for the observed pK(a) shifts. The calculations for HIV protease agree reasonably well with experiment, despite the complexity of the system. The present computational approach should be useful for a variety of other applications.