Theoretical study on the HIV-1 integrase inhibitor 1-(5-chloroindol-3-yl)-3-hydroxy-3-(2H-tetrazol-5-yl)-propenone (5CITEP)

1-(5-Chloroindol-3-yl)-3-hydroxy-3-(2H-tetrazol-5-yl)-propenone (5CITEP) is an inhibitor of the HIV-1 integrase (IN). Theoretical studies were performed on the interaction of this inhibitor with surrounding amino acids. Density functional theory (DFT) calculations were conducted to identify the protonation state of HIV-1 integrase (IN), in particular, residues Lys156 and Lys159 and 5CITEP inhibitor. The results indicate that the both lysine residues are in protonated forms while 5CITEP is in de-protonated form. The binding energy of 5CITEP and its six surrounding amino acids, i.e., Thr66, Gln148, Glu152, Asn155, Lys156, and Lys159 is −41.33 kcal/mol. In addition, conformation analysis of 5CITEP was carried out to determine conformational minima of this compound. The calculations reveal that the lowest energy conformation of 5CITEP is close to that of X-ray conformation, as evidenced by energy difference of 1.5 kcal/mol only.