Folding@home: achievements from over twenty years of citizen science herald the exascale eraSimulations of biomolecules have enormous potential to inform our
understanding of biology but require extremely demanding calculations. For over
twenty years, the Folding@home distributed computing project has pioneered a
massively parallel approach to biomolecular simulation, harnessing the
resources of citizen scientists across the globe. Here, we summarize the
scientific and technical advances this perspective has enabled. As the
project's name implies, the early years of Folding@home focused on driving
advances in our understanding of protein folding by developing statistical
methods for capturing long-timescale processes and facilitating insight into
complex dynamical processes. Success laid a foundation for broadening the scope
of Folding@home to address other functionally relevant conformational changes,
such as receptor signaling, enzyme dynamics, and ligand binding. Continued
algorithmic advances, hardware developments such as GPU-based computing, and
the growing scale of Folding@home have enabled the project to focus on new
areas where massively parallel sampling can be impactful. While previous work
sought to expand toward larger proteins with slower conformational changes, new
work focuses on large-scale comparative studies of different protein sequences
and chemical compounds to better understand biology and inform the development
of small molecule drugs. Progress on these fronts enabled the community to
pivot quickly in response to the COVID-19 pandemic, expanding to become the
world's first exascale computer and deploying this massive resource to provide
insight into the inner workings of the SARS-CoV-2 virus and aid the development
of new antivirals. This success provides a glimpse of what's to come as
exascale supercomputers come online, and Folding@home continues its work.
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