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Author(s)
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Bhati, Agastya P (University Coll. London) ; Wan, Shunzhou (U. Coll. London) ; Alfè, Dario (U. Coll. London) ; Clyde, Austin R (Chicago U.) ; Bode, Mathis (RWTH Aachen U.) ; Tan, Li (Brookhaven Natl. Lab.) ; Titov, Mikhail (Rutgers U., Piscataway) ; Merzky, Andre (Rutgers U., Piscataway) ; Turilli, Matteo (Rutgers U., Piscataway) ; Jha, Shantenu (Brookhaven Natl. Lab. ; Rutgers U., Piscataway) ; Highfield, Roger R (Unlisted, GB) ; Rocchia, Walter (Italian Inst. Tech., Genoa) ; Scafuri, Nicola (Italian Inst. Tech., Genoa) ; Succi, Sauro (Italian Inst. Tech., Genoa) ; Kranzlmüller, Dieter (Leibniz Rechenzentrum, Garching) ; Mathias, Gerald (Leibniz Rechenzentrum, Garching) ; Wifling, David (Leibniz Rechenzentrum, Garching) ; Donon, Yann (CERN) ; Di Meglio, Alberto ; Vallecorsa, Sofia (CERN) ; Ma, Heng (Argonne) ; Trifan, Anda (Argonne) ; Ramanathan, Arvind (Argonne) ; Brettin, Tom (Argonne) ; Partin, Alexander (Argonne) ; Xia, Fangfang (Argonne) ; Duan, Xiaotan (Chicago U.) ; Stevens, Rick (Argonne) ; Coveney, Peter V (U. Coll. London ; Amsterdam U.) |
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Abstract
| The race to meet the challenges of the global pandemic has served
as a reminder that the existing drug discovery process is expensive, inefficient
and slow. There is a major bottleneck screening the vast number of potential
small molecules to shortlist lead compounds for antiviral drug development.
New opportunities to accelerate drug discovery lie at the interface between
machine learning methods, in this case, developed for linear accelerators,
and physics-based methods. The two in silico methods, each have their own
advantages and limitations which, interestingly, complement each other.
Here, we present an innovative infrastructural development that combines
both approaches to accelerate drug discovery. The scale of the potential resulting workflow is such that it is dependent on supercomputing to achieve
extremely high throughput. We have demonstrated the viability of this workflow for the study of inhibitors for four COVID-19 target proteins and our
ability to perform the required large-scale calculations to identify lead antiviral compounds through repurposing on a variety of supercomputers. |