FSDscore: An Effective Target‐focused Scoring Criterion for Virtual Screening

Abstract

Improving screening efficiency is one of the most challenging tasks of virtual screening (VS). In this work, we propose an effective target-focused scoring criterion for VS and apply it to the screening of a specific target scaffold replacement library constructed by enumeration of suitable substitution fragments and R-groups of known ligands. This criterion is based on both ligand-and structure-based scoring methods, which includes feature maps, 3D shape similarity, and the pairwise distance information between proteins and ligands (FSDscore). It is precisely due to the hybrid advantages of ligand-and structure-based approaches that FSDscore performs far better on the validation dataset than other scoring methods. We apply FSDscore to the VS of different kinase targets, MERTK (Mer tyrosine kinase) and ABL1 (tyrosine-protein kinase ABL1) in order to avoid occasionality. Finally, a VS case study shows the potential and effectiveness of our scoring criterion in drug discovery and molecular dynamics simulation further verifies its powerful ability.