LABORATORY INFORMATICS
Potential drug candidates found using VirtualFlow g
platform, in a March 2020 issue of Nature. ‘In my dissertation I demonstrated mathematically that scaling up really does improve the hit rate,’ Gorgulla stressed. ‘What’s particularly nice about this is that the solution scales linearly, so if you double the number of processors, you double the screening power.’ Importantly, VirtualFlow has been developed to optimise functions, such as writing files to file systems, which might otherwise represent bottlenecks for screening on such a massive scale. The VirtualFlow software can carry out
screens in a series of stages. The first screening stage identifies compounds that bind to the designated target, and sequential screens can hone the list of initial hits by imposing increasingly stringent binding attributes, through
“We validated the software on the Harvard computing cluster, which includes more than 30 000 processing cores”
calculations of exactly how each molecule will fit and bind to the target under different conditions. The program also assesses each potential 3D conformation of each drug molecule, which may change under different cellular conditions. The top few hundred hits can then be tested experimentally, which dramatically saves on lab time, and also improves the likely hit rate. The team’s published paper in Nature
describes development of the VirtualFlow platform and the mathematical model that demonstrate this ability to improve hit rate. The paper also outlines a use case through which the software was used to screen a ready-to-dock ligand library – also prepared by Gorgulla –to identify and experimentally validate compounds that would inhibit a target enzyme. The curated library contains more than 1.4 billion commercially available molecules for which the 3D structures have been calculated. ‘We validated the software on the
Harvard computing cluster, which includes more than 30,000 processing cores, and it took around two weeks to complete the screen on this library of 1.4 billion compounds using around 8,000 of these cores,’ Arthanari said.
Virtual flow workflow 26 Scientific Computing World Summer 2020 @scwmagazine |
www.scientific-computing.com
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