Surely you are joking, Mr Docking!
Francesco Gentile, Tudor I. Oprea, Alexander Tropsha, Artem Cherkasov
Abstract
In the wake of recent COVID-19 pandemics scientists around the world rushed to deliver numerous CADD (Computer-Aided Drug Discovery) methods and tools that could be reliably used to discover novel drug candidates against the SARS-CoV-2 virus. With that, there emerged a trend of a significant democratization of CADD that contributed to the rapid development of various COVID-19 drug candidates currently undergoing different stages of validation. On the other hand, this democratization also inadvertently led to the surge rapidly performed molecular docking studies to nominate multiple scores of novel drug candidates supported by computational arguments only. Albeit driven by best intentions, most of such studies also did not follow best practices in the field that require experience and expertise learned through multiple rigorously designed benchmarking studies and rigorous experimental validation. In this Viewpoint we reflect on recent disbalance between small number of rigorous and comprehensive studies and the proliferation of purely computational studies enabled by the ease of docking software availability. We further elaborate on the hyped oversale of CADD methods' ability to rapidly yield viable drug candidates and reiterate the critical importance of rigor and adherence to the best practices of CADD in view of recent emergence of AI and Big Data in the field.