Fostering discoveries in the era of exascale computing: How the next generation of supercomputers empowers computational and experimental biophysics alike

Over a century ago, physicists started broadly relying on theoretical models to guide new experiments. Soon thereafter, chemists began doing the same. Now, biological research enters a new era when experiment and theory walk hand in hand. Novel software and specialized hardware became essential to understand experimental data and propose new models. In fact, current petascale computing resources already allow researchers to reach unprecedented levels of simulation throughput to connect in silico and in vitro experiments. The reduction in cost and improved access allowed a large number of research groups to adopt supercomputing resources and techniques. Here, we outline how large-scale computing has evolved to expand decades-old research, spark new research efforts, and continuously connect simulation and observation. For instance, multiple publicly and privately funded groups have dedicated extensive resources to develop artificial intelligence tools for computational biophysics, from accelerating quantum chemistry calculations to proposing protein structure models. Moreover, advances in computer hardware have accelerated data processing from single-molecule experimental observations and simulations of chemical reactions occurring throughout entire cells. The combination of software and hardware has opened the way for exascale computing and the production of the first public exascale supercomputer, Frontier, inaugurated by the Oak Ridge National Laboratory in 2022. Ultimately, the popularization and development of computational techniques and the training of researchers to use them will only accelerate the diversification of tools and learning resources for future generations.