Accurate approximation of electrostatic energies is of major importance for our understanding protein energetics in computer-aided drug design as well as for the design of novel biocatalysts and protein therapeutics. In this study, we applied new method, based on an aspherical atom model build from University at Buffalo Database (UBDB), for estimating electrostatic interactions in HIV protease (HIV-PR). The method is much more accurate than classically used force fields. HIV-PR, an aspartyl protease enzyme involved in human immunodeficiency virus (HIV) replication, is an important target for drug design strategies to combat acquired immune deficiency syndrome (AIDS). Most of the currently used HIV-PR inhibitors in HIV treatment have been prone to suffer from the mutations associated with drug resistance. Therefore, it is necessary to search for potent alternatives helping to overcome the resistance. The active site of PR protein is formed by the dimerization of the two monomers and covered by two glycine rich, antiparallel beta-hairpins flaps. In recent study, it has been shown that monomeric HIV-PR is relatively stable as compared to its dimeric form. It is also reported that mutations at or near the monomer-monomer interface shift the monomer-dimer equilibrium to inactive monomeric form, which is now of much interest in the contexts of drug design. Such observation can be confirmed by applying molecular dynamics simulation providing ample insights into both biological and technical aspect of macromolecular conformation and dynamics at atomistic level. So it's worth to investigate the multi-conformers of HIV-PR existing due to various mutations by combining MD simulation with the UBDB derived electron density for high resolution structures ≈0.8-1.00 A. The research may lead to the discovery of a general rule of conserved electrostatic interaction that stabilizes the HIV-PR dimer.