Binding site druggability assessment in fragment-based drug design

Abstract

Target druggability refers to the propensity that a particular target is amenable to bind high-affinity drug- like molecules. A robust yet accurate computational assessment of target druggability would greatly benefit the fields of chemical genomics and drug discovery. Here, we illustrate a structure-based computational protocol to quantitatively assess the target binding-site druggability via in silico screening a fragment-like compound library. In particular, we provide guidelines, suggestions, and critical thoughts on different aspects of this computational protocol, including: construction of fragment library, preparation of target structure, in silico fragment screening, and analysis of druggability.