Evaluating AutoGrow4–an open-source toolkit for semi-automated computer-aided drug discovery

Introduction: Drug discovery is a long and expensive process characterized by a high failure rate. To make this process more rational and efficient, scientists always look for new and better ways to design novel ligands for a target of interest. Among different approaches, de novo ones gained popularity in the last decade, thanks to their ability to efficiently explore the chemical space and their increasing reliability in generating high-quality compounds. Autogrow4 is open-source software for de novo drug design that generates ligands for a given target by exploiting a combination of a genetic algorithm and molecular docking calculations. Areas Covered: In the present paper, the authors dissect this program’s usefulness and limitations in generating new compounds from a pharmacodynamic and pharmacokinetic perspective. Specifically, this article examines all reported applications of the Autogrow code in the literature (as retrieved from the Scopus database) from the release of its first version in 2009 to the present. Expert Opinion: In the hands of an expert molecular modeler, Autogrow4 is a useful tool for de novo ligand design. Its modular and open-source codebase offers many protocol customization features. The main downsides are limited control over the pharmacokinetic features of generated ligands and the bias toward high molecular weight compounds.