Tang, S.; Ding, J.; Zhu, X.; Wang, Z.; Zhao, H.; Wu, J.

AutoDock Vina and its derivatives have established themselves as a prevailing pipeline for virtual screening in contemporary drug discovery. Our Vina-GPU method leverages the parallel computing power of GPUs to accelerate AutoDock Vina, and Vina-GPU 2.0 further enhances the speed of AutoDock Vina and its derivatives. Given the prevalence of large virtual screens in modern drug discovery, the improvement of speed and accuracy in virtual screening has become a longstanding challenge. In this study, we propose Vina-GPU 2.1, aimed at enhancing the docking speed and precision of AutoDock Vina and its derivatives through the integration of novel algorithms to facilitate improved docking and virtual screening outcomes. Building upon the foundations laid by Vina-GPU 2.0, we introduce a novel algorithm, namely Reduced Iteration and Low Complexity BFGS (RILC-BFGS), designed to expedite the most time-consuming operation. Additionally, we implement grid cache optimization to further enhance the docking speed. Furthermore, we employ optimal strategies to individually optimize the structures of ligands, receptors, and binding pockets, thereby enhancing the docking precision. To assess the performance of Vina-GPU 2.1, we conduct extensive virtual screening experiments on three prominent targets, utilizing two fundamental compound libraries and seven docking tools. Our results demonstrate that Vina-GPU 2.1 achieves an average 4.97-fold acceleration in docking speed and an average 342% improvement in EF1% compared to Vina-GPU 2.0. The source code and tools for Vina-GPU 2.1 are freely available at https://github.com/DeltaGroupNJUPT/Vina-GPU-2.1, accompanied by comprehensive instructions and illustrative examples.