[In-silico approaches for fragment-based drug design]

Abstract

An important step to promote fragment-based drug design (FBDD) is to find high-quality fragment molecules. Therefore the design of the fragment library is the most crucial stage. In our fragment library, the main considerations are ligand efficiency (LE), diversity, and solubility with drug-like properties. We especially considered LE to raise hit probability in screening. We estimated LE of the fragment molecule based on known LE values of the active compounds. We also developed a docking program suitable for screening fragments rather than drug compounds. Furthermore, we explored fragment-linking program, which links together fragments that bind to adjacent sites on a target protein so as to promote FBDD in silico.