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

Abstract

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 structure database. The original implementation of SDO-VS involved PMs with only sp 3 -hybridized carbon atoms. However, utilization of sp 2 -and sp-hybridized atoms and/or small molecular fragments, in addition to sp 3 -hybridized atoms, is expected to provide more efficient screening. To this end, this study investigated the effect of sp 3 -, sp 2 -, 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 proteins. Overall, this new method improved screening efficiencies, as measured by the area under the curve of the corresponding receiver operating characteristic plots.