DeepCOMO: from structure-activity relationship diagnostics to generative molecular design using the compound optimization monitor methodology

Abstract

AbstractThe compound optimization monitor (COMO) approach was originally developed as a diagnostic approach to aid in evaluating development stages of analog series and progress made during lead optimization. COMO uses virtual analog populations for the assessment of chemical saturation of analog series and has been further developed to bridge between optimization diagnostics and compound design. Herein, we discuss key methodological features of COMO in its scientific context and present a deep learning extension of COMO for generative molecular design, leading to the introduction of DeepCOMO. Applications on exemplary analog series are reported to illustrate the entire DeepCOMO repertoire, ranging from chemical saturation and structure–activity relationship progression diagnostics to the evaluation of different analog design strategies and prioritization of virtual candidates for optimization efforts, taking into account the development stage of individual analog series.