For the expensive cost of synthesizing new compounds, the accuracy of protein-ligand binding affinity prediction become very important in de novo drug design process compared to virtual screening methods. We found a series of properties that affect binding affinity beyond usual force fields and scoring functions, including binding stability, lock-key matching and hydrophobic/hydrophilic matching. Binding stability refer to the force stability of ligand settling in the binding site; lock-key matching refer to the geometry complementarities between ligand and binding site; hydrophobic/hydrophilic matching refer to the nonpolarity/polarity matching between ligand and protein. We found that these criterions were highly correlated with whether the ligand could bind to the receptors by analyzing the DUD dataset (Directory of Useful Decoys, including 40 therapeutic interested targets). So we can eliminate designed molecules with these new criterions to select some more reliable molecules for afterwards synthesizing.

Post-filter in de novo drug design

243rd National Meeting (2012)

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