Addressing docking pose selection with structure-based deep learning: Recent advances, challenges and opportunities
Abstract
Molecular docking is a widely used technique in drug discovery to predict the binding mode of a given ligand to its target. However, the identification of the near-native binding pose in docking experiments still represents a challenging task as the scoring functions currently employed by docking programs are parametrized to predict the binding affinity, and, therefore, they often fail to correctly identify the ligand native binding conformation. Selecting the correct binding mode is crucial to obtaining meaningful results and to conveniently optimizing new hit compounds. Deep learning (DL) algorithms have been an area of a growing interest in this sense for their capability to extract the relevant information directly from the protein-ligand structure. Our review aims to present the recent advances regarding the development of DL-based pose selection approaches, discussing limitations and possible future directions. Moreover, a comparison between the performances of some classical scoring functions and DL-based methods concerning their ability to select the correct binding mode is reported. In this regard, two novel DL-based pose selectors developed by us are presented.
Davide Gadioli
Assistant Professor
He earned his M.S. in Information Technology (2013) and Ph.D. cum laude in 2019 from Politecnico di Milano. A former Visiting Student at IBM Research (2015), he is now a postdoctoral researcher at DEIB, focusing on application autotuning, approximate computing, molecular docking, and drug discovery. He contributes to EXSCALATE software development.
Gianluca Palermo
Full Professor
Gianluca Palermo received the M.Sc. degree in Electronic Engineering in 2002, and the Ph.D degree in Computer Engineering in 2006 from Politecnico di Milano. He is currently an associate professor at Department of Electronics and Information Technology in the same University. Previously he was also consultant engineer in the Low Power Design Group of AST – STMicroelectronics working on network on-chip and research assistant at the Advanced Learning and Research Institute (ALaRI) of the Università della Svizzera italiana (Switzerland). His research interests include design methodologies and architectures for embedded and HPC systems, focusing on AutoTuning aspects.