QM-based refinement calculation based on density functional theory
(DFT) calculations as described above (Eq. 8). The best-ranked 180 compounds
from the screening were sorted for further inspection. To select a diverse set of
structures for the biochemical assays, these compounds were clustered according to
the structural similarity. Of the 50 structural clusters, 25 structurally diverse compounds, with the best scores, were chosen and purchased from the chemical vendor
(www.specs.net) to be tested against the HIV RT-associated RNase H function in
enzymatic assays. The overall workflow of the virtual screening process is shown
in Fig. 4. Out of 25 compounds tested, 3 compounds inhibited the RNase H activity
Fig. 3 Structure of HIV-1 reverse transcriptase enzyme and its active site. The components of the
QM and MM region for geometry optimization are shown
Fig. 4 Overall workflow of structure-based virtual screening strategies applied. Initial hit
molecules from the first screening are provided and one of the compound is highlighted in regions
where it shares a common structural pattern with known RNase H inhibitor BHMP07
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