Threshold interaction energy of NRTIʹs (2′-deoxy 3′-substituted nucleosidic analogs of reverse transcriptase inhibitors) to undergo competitive inhibition

A quantum pharmacological study has been carried out on nucleosidic inhibitors for HIV-1RT where ab initio HF molecular orbital calculations in conjunction with other quantum mechanical techniques have been utilized in a systematic manner to understand the pharmacophoric features and evaluate specific drug–receptor interactions. The interaction energy between the drug and the closest asp 185 of the catalytic triad has been indicated to be crucial in determining the potency of the nucleosidic drug. This study also emphasizes on identifying important specific drug–receptor interactions and evaluating them at the microscopic level to understand the potency regulation as minor conformational changes may lead to significant difference in interaction energies. Although based on relatively few points our correlation of interaction energies with potency data indicates requirement of 13 kcal/mol threshold interaction energy for the drug to undergo efficient competitive inhibition.