AutoDock Koto: A Gradient Boosting Differential Evolution for Molecular Docking

Molecular docking plays a vital role in modern drug discovery, by supporting predictions of the binding modes and affinities of ligands at the binding site of target proteins. Several docking programs have been developed for both commercial and academic applications. Typically, a docking program’s performance depends on the sampling algorithm used to generate the ligand’s potential conformations and the scoring function applied to evaluate and rank these conformations. Evolutionary algorithms are widely used as sampling algorithms in docking programs. However, both the linkage problem and the dimensionality degenerate the search ability of evolutionary algorithms in the docking process. Therefore, a newly designed docking program named AutoDock Koto was developed in this study, which adopts a novel gradient boosting differential evolution algorithm to effectively address these issues. Experimental results show that compared with commonly used docking programs, AutoDock Koto yields dramatic improvements in docking performance based on an extensive dataset of 285 protein–ligand complexes. In addition, due to its strong docking ability, AutoDock Koto was used to identify potential drugs for COVID-19 based on a virtual screening of all approved drugs in our experiments. Sixteen drugs are found to possess low binding energy to the main target protease of SARS-CoV-2 and, thus, have the potential to treat COVID-19 as antiviral drugs. The source code of AutoDock Koto can be downloaded for free from https://github.com/codezhouj/Molecular_Docking.

I. Introduction

Computer-aided drug design (CADD) techniques have become reliable and essential tools in modern drug design. The discovery and development of novel drugs are typically expensive and time consuming, while CADD can significantly accelerate the screening pace and drastically improve hit discovery rates [1]. In fact, most pharmaceutical companies operate CADD departments, and many commercial drugs have been developed through the use of CADD, such as saquinavir, indinavir, captopril, and tirofiban [2], [3].