Molecular docking is a pragmatic approach to exploit
protein structures
for new ligand discovery, but the growing size of available chemical
space is increasingly challenging to screen on in-house computer clusters.
We have therefore developed AWS-DOCK, a protocol for running UCSF
DOCK in the AWS cloud. Our approach leverages the low cost and scalability
of cloud resources combined with a low-molecule-cost docking engine
to screen billions of molecules efficiently. We benchmarked our system
by screening 50 million HAC 22 molecules against the DRD4 receptor
with an average CPU time of around 1 s per molecule. We saw up to
3-fold variations in cost between AWS availability zones. Docking
4.5 billion lead-like molecules, a 7 week calculation on our 1000-core
lab cluster, runs in about a week depending on accessible CPUs, in
AWS for around $25,000, less than the cost of two new nodes. The cloud
docking protocol is described in easy-to-follow steps and may be sufficiently
general to be used for other docking programs. All the tools to enable
AWS-DOCK are available free to everyone, while DOCK 3.8 is free for
academic research.