Abstract

Study of forces governing the drug-receptor interaction of tetrahydroimidazodiazepinones (HIV-1-NNRTIs):A theoretical formalism

Author(s): V.K.Sahu, A.K.R.Khan, R.K.Singh, P.P.Singh

To study various forces governing the drug-receptor interaction of a series of Tetrahydroimidazodiazepinones with their receptor, we have evaluated Log P and SASA for measurement of hydrophobic interaction; energy of protonation (TE) for measurement of most favorable hydrogen bond acceptor site; bond length and bond strain for measurement of strength of hydrogen bond formed between drug and receptor; atomic charges, ionization potential (IP), electronegativity (), acidic (E#n) and basic atomic softness (E#m) and their difference (E# nm) for measurement of elactrostatic interaction. The molecularmodeling and geometry optimization of the compounds and receptorÂÂÂ’s aminoacids (Val, Met and Tyr) have been done by MOPAC-2002 associatedwithCaChe software. SoftnessCalculator has been used to evaluate effective atomic softness (E‡n and E#m). The study have shown that hydrophobic interaction is predominant and made major contribution, while hydrogen bonding and polar interactions help in proper orientation of the compound (or its functional groups) tomakemaximaminteraction. The overall strengths of these bonds determine the degree of affinity between the drug and the receptor.