Drug-resistant mutants of HIV-1 protease limit the long-term effectiveness of current anti-viral therapy. In order to study drug resistance, the wild-type HIV-1 protease and the mutants R8Q, V32I, M46I, V82A, V82I, V82F, I84V, V32I/I84V and M46I/I84V were modeled with the inhibitors saquinavir and indinavir using the program AMMP. A new screen term was introduced to reproduce more correctly the electron distribution of atoms. The atomic partial charge was represented as a delocalized charge distribution instead of a point charge. The calculated protease-saquinavir interaction energies showed the highly significant correlation of 0.79 with free energy differences derived from the measured inhibition constants for all 10 models. Three different protonation states of indinavir were evaluated. The best indinavir model included a sulfate and gave a correlation coefficient of 0.68 between the calculated interaction energies and free energies from inhibition constants for nine models. The exception was R8Q with indinavir, probably due to differences in the solvation energy. No significant correlation was found using the standard molecular mechanics terms. The incorporation of the new screen correction resulted in better prediction of the effects of inhibitors on resistant protease variants and has potential for selecting more effective inhibitors for resistant virus.