AUTHOR=Souza Paulo C. T. , Limongelli Vittorio , Wu Sangwook , Marrink Siewert J. , Monticelli Luca TITLE=Perspectives on High-Throughput Ligand/Protein Docking With Martini MD Simulations JOURNAL=Frontiers in Molecular Biosciences VOLUME=8 YEAR=2021 URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2021.657222 DOI=10.3389/fmolb.2021.657222 ISSN=2296-889X ABSTRACT=

Molecular docking is central to rational drug design. Current docking techniques suffer, however, from limitations in protein flexibility and solvation models and by the use of simplified scoring functions. All-atom molecular dynamics simulations, on the other hand, feature a realistic representation of protein flexibility and solvent, but require knowledge of the binding site. Recently we showed that coarse-grained molecular dynamics simulations, based on the most recent version of the Martini force field, can be used to predict protein/ligand binding sites and pathways, without requiring any a priori information, and offer a level of accuracy approaching all-atom simulations. Given the excellent computational efficiency of Martini, this opens the way to high-throughput drug screening based on dynamic docking pipelines. In this opinion article, we sketch the roadmap to achieve this goal.