ABSTRACT
The social and economic impact of the COVID-19 pandemic demands a reduction of the time required to find a therapeutic cure. In this paper, we describe the EXSCALATE molecular docking platform capable to scale on an entire modern supercomputer for supporting extreme-scale virtual screening campaigns. Such virtual experiments can provide in short time information on which molecules to consider in the next stages of the drug discovery pipeline, and it is a key asset in case of a pandemic. The EXSCALATE platform has been designed to benefit from heterogeneous computation nodes and to reduce scaling issues. In particular, we maximized the accelerators' usage, minimized the communications between nodes, and aggregated the I/O requests to serve them more efficiently. Moreover, we balanced the computation across the nodes by designing an ad-hoc workflow based on the execution time prediction of each molecule. We deployed the platform on two HPC supercomputers, with a combined computational power of 81 PFLOPS, to evaluate the interaction between 70 billion of small molecules and 15 binding-sites of 12 viral proteins of SARS-CoV-2. The experiment lasted 60 hours and it performed more than one trillion ligand-pocket evaluations, setting a new record on the virtual screening scale.
ABSTRACT
Drug repurposing is a cost-effective process to identify therapeutic candidates during a medical crisis or pandemic. The supercomputing platform, EXaSCale smArt pLatform Against paThogEns for CoronaVirus (EXSCALATE4CoV;E4C), was used to identify drug candidates for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. E4C identified raloxifene as having great therapeutic potential, confirmed by in vitro data, which led to the progression of clinical trials to assess its efficacy. Raloxifene met the primary virologic endpoint in the treatment of early mild coronavirus disease 2019 (COVID-19), and although additional clinical trials are needed to confirm these results, there is evidence in support of in silico drug repurposing to provide cost-effective and rapid drug screening to identify treatment options for the pandemic and future pandemics. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.
ABSTRACT
Virtual screening is one of the early stages that aims to select a set of promising ligands from a vast chemical library. Molecular Docking is a crucial task in the process of drug discovery and it consists of the estimation of the position of a molecule inside the docking site. In the contest of urgent computing, we designed from scratch the EXSCALATE molecular docking platform to benefit from heterogeneous computation nodes and to avoid scaling issues. This poster presents the achievements and ongoing development of the EXSCALATE platform, together with an example of usage in the context of the COVID-19 pandemic.
ABSTRACT
The social and economic impact of the COVID-19 pandemic demands a reduction of the time required to find a therapeutic cure. In this paper, we describe the EXSCALATE molecular docking platform capable to scale on an entire modern supercomputer for supporting extreme-scale virtual screening campaigns. Such virtual experiments can provide in short time information on which molecules to consider in the next stages of the drug discovery pipeline, and it is a key asset in case of a pandemic. The EXSCALATE platform has been designed to benefit from heterogeneous computation nodes and to reduce scaling issues. In particular, we maximized the accelerators’usage, minimized the communications between nodes, and aggregated the I/O requests to serve them more efficiently. Moreover, we balanced the computation across the nodes by designing an ad-hoc workflow based on the execution time prediction of each molecule. We deployed the platform on two HPC supercomputers, with a combined computational power of 81 PFLOPS, to evaluate the interaction between 70 billion of small molecules and 15 binding-sites of 12 viral proteins of SARS-CoV-2. The experiment lasted 60 hours and it performed more than one trillion ligand-pocket evaluations, setting a new record on the virtual screening scale. IEEE