An open-source drug discovery platform enables ultra-large virtual screens.

Nature
Christoph GorgullaHaribabu Arthanari

Abstract

On average, an approved drug currently costs US$2-3 billion and takes more than 10 years to develop1. In part, this is due to expensive and time-consuming wet-laboratory experiments, poor initial hit compounds and the high attrition rates in the (pre-)clinical phases. Structure-based virtual screening has the potential to mitigate these problems. With structure-based virtual screening, the quality of the hits improves with the number of compounds screened2. However, despite the fact that large databases of compounds exist, the ability to carry out large-scale structure-based virtual screening on computer clusters in an accessible, efficient and flexible manner has remained difficult. Here we describe VirtualFlow, a highly automated and versatile open-source platform with perfect scaling behaviour that is able to prepare and efficiently screen ultra-large libraries of compounds. VirtualFlow is able to use a variety of the most powerful docking programs. Using VirtualFlow, we prepared one of the largest and freely available ready-to-dock ligand libraries, with more than 1.4 billion commercially available molecules. To demonstrate the power of VirtualFlow, we screened more than 1 billion compounds and identified a set of structura...Continue Reading

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Citations

May 21, 2020·The New England Journal of Medicine·Jerry M Parks, Jeremy C Smith
Jun 23, 2020·Briefings in Bioinformatics·Louison Fresnais, Pedro J Ballester
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Methods Mentioned

BETA
NMR
surface
nuclear magnetic resonance
dynamic light scattering
size-exclusion chromatography
Biosensors
chip

Software Mentioned

GCP
VirtualFlow
Open Babel
Moab
Smina Vinardo
AutoDock Vina
VFLP VirtuaFlow for VirtualFlow for
SciPy library
Vina
molconvert

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