Articles

When a drug interacts with its receptor, the nonpolar substituent of drug and receptor proteins attract each other because they have opposite magnitude with respect to each other. X-rays structure studies reflected that the S2/S2’ pocket in HIV-1 protease enzyme are essentially hydrophobic. The residues that make up these pockets are Val-32, Ile-47, Ile-50, and Ile-84 in each monomeric polypeptidic unit of the protease enzyme. Δπ_dr and ΔSASA_dr have been used to measure the extent of hydrophobic interaction between peptidic protease inhibitors and receptor proteins (binding site: valine‒isoleucine; and catalytic site: glycine‒aspartic acid‒threonine) on the HIV-1 protease enzyme. For measurement of hydrophobic interaction, the molecular modeling and geometry optimization of all the inhibitors and the receptor amino acids have been carried out with CAChe Pro software by opting semiempirical PM3 methods. Log P was calculated using the atom-typing scheme of Ghose and Crippen, while solvent accessible surface area by conductor likes screening model. π_d, π_r, SASA_Sd and SASA_Srwell describe the hydrophobicities of the substituents and play the effective role for site selectivity for interaction of the drug with the receptor. Comparative study of values of Δπ_dr and ΔSASA_dr show the order of hydrophobic interaction with respect to amino acids: Asp > Thr > Val > Ile and Thr > Val > Asp > Ile, respectively. Further, comparative study of the values of (ΣΔπ_dr)_binding-site, (ΣΔπ_dr)_{catalytic-site}, (ΣΔSASA_dr)_binding-site, (ΣΔSASA_dr)_{catalytic-site} shows that peptidic HIV-1-PRIs interact with binding site rather than catalytic site as binding site have lower value of ΣΔπ_dr and ΣΔSASA_dr. Among the binding site, Val has maximum interaction than Ile, as it has lower vale of Δπ_dr and ΔSASA_dr.