Improvement of Pseudo-molecule Generation on Solvent Dipole Ordering Virtual Screening (SDO-VS)

Solvent dipole ordering virtual screening (SDO-VS) is a virtual screening method that focuses on the shape of the SDO region at the binding site of the protein. In SDO-VS, pseudo molecules (PMs) are generated to reproduce the shape of the SDO region. Compounds that have shapes (or volumes) similar to those of the PMs are then screened from a 3D struct ure database. The original implementation of SDO-VS involved PMs with only sp 3-hybridized carbon atoms. However, utilization of s p2and sp-hybridized atoms and/or small molecular fragments, in addition to sp 3-hybridized atoms, is expected to provide more effi cient screening. To this end, this study investigated the effect of sp3-, sp2-, and sp-hybridized atoms and phenyl rings as fragments for PM generation in the SDO-VS method. The screening efficiencies were compared with the original method for several drug target pr oteins. Overall, this new method improved screening efficiencies, as measured by the area under the cur v of the corresponding receiver operating characte istic plots.