Recently, we have studied drug-receptor interaction of the peptidic HIV-1 protease inhibitors based on polar and hydrophobic interactions. We have also studied pharmacokinetics of these inhibitors based on Lipinski’s rule of five and its extended form. After that there was a need to study intermolecular interactions. From literatures, drug-receptor interaction involves hydrogen bonds between acceptor and donor sites of drug and its receptor. These donor acceptor sites must be more than four to be dominant. As single intermolecular H-bond is relatively weak and unlikely to support this type of interaction. It is also clear from literature that this interaction contribute to the alignment of reacting species in proper three-dimensional space in such a position that strong and effective polar or hydrophobic or both interaction occurs to form drug-receptor adduct or enzyme inhibitor complex as appropriate. The strength of H-bonds formed between drug and receptor was judged by bond lengths, bond angles and bond orders. As well as, its nature (strong, moderate or weak) and its number, too. Along with H-bonding, we have also studied Van der Walls i.e. non-bonding type interaction. These non-bonding interactions were studied using charge transfer from donor to acceptor and this results transfer of electron flux from donor molecule (drug/receptor) towards acceptor (receptor/ drug). Thus, lowering of energy of the system under investigation will occur. For this resulted interaction energy was also studied that very clearly explain feasibility of interactions. As we know that all above phenomena are molecular properties and do not cover involvement of orbitals. To cover this we have also studied drug-receptor interaction involving molecular orbital. It was HOMO of one reacting molecule (B) that donates electron pair, electron cloud or electron density to LUMO of another reacting molecule (A) that accepts or accommodates this electron pair, electron cloud or electron density. The quantity of the electron flux from HOMO to LUMO was judged by the value of ∆E<SUB>LH</SUB>. A lower value of this will support strong and effective drug-receptor interaction. Results of orbital based study have also been found to supports the results as abstracted from interaction energy.
