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Quantum chemical-based drug–receptor interaction of tetrahydroimidobenzodiazepinones (HIV-1-NNRTIs) with receptor (HIV-1-NNRTI-binding pocket)

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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 (ΔE) 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; ΔE ‡ nm  = ∣E ‡ n  − E ‡ m ∣ 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 and E ‡ m ). 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.

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  1. Department of Chemistry, Maharani Lal Kunwari Post Graduate College, Balrampur, U.P., India

    Ahmad Khalid Raza Khan, Suhail Ahmad Khan & Mohiuddin Ansari

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  1. Ahmad Khalid Raza Khan
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  2. Suhail Ahmad Khan
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  3. Mohiuddin Ansari
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Correspondence to Ahmad Khalid Raza Khan.

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Khan, A.K.R., Khan, S.A. & Ansari, M. Quantum chemical-based drug–receptor interaction of tetrahydroimidobenzodiazepinones (HIV-1-NNRTIs) with receptor (HIV-1-NNRTI-binding pocket). Med Chem Res 20, 231–238 (2011). https://doi.org/10.1007/s00044-010-9298-1

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  • DOI: https://doi.org/10.1007/s00044-010-9298-1

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