Abstract
The chemical forces responsible for interaction of drug (HIV-1-NNRTI) with receptor (HIV-1-NNRTI-binding pocket) have been studied by evaluating log P and SASA for the measurement of hydrophobic interaction; energy of protonation (Delta E) for the measurement of most favorable hydrogen bond acceptor site; bond length and bond strain for the measurement of strength of hydrogen bond formed between drug and receptor; Delta E (nm) (aEuro) = a E pound (n) (aEuro) - E (m) (aEuro) a pound for the measurement of polar interaction. The molecular modeling and geometry optimization of the compounds (drugs) and receptor amino acids (Val, Met, and Tyr) have been done using MOPAC-2002 associated with CAChe software. Softness Calculator has been used to evaluate effective atomic softness (E (n) (aEuro) and E (m) (aEuro) ). The results indicate that there is strong and effective hydrophobic interaction between hydrophobic substituent at site-6 of the drug and Val-Y187 of the receptor; hydrophobic substituent at site-5 and Met-Y184. Similarly, hydrogen bonds are formed between N-atom (site-6) of the drug and H-atom of the phenolic group of the Tyr-Y188; between phenolic group of the Tyr-181 and H-atom (site-1) of the drug. Polar interaction (charge transfer) occurs between -C=O/S (site-2) of the drug and -CONH- of Asn-Y182-Tyr-Y183.