A fundamental challenge in biological research is achieving an atomic-level description and mechanistic understanding of the function of biomolecules. Techniques for biomolecular simulations have undergone substantial developments, and their accuracy and scope have expanded considerably. Progress has been made through an increasingly tight integration of experiments and simulations, with experiments being used to refine simulations and simulations used to interpret experiments. Here we review the underpinnings of this progress, including methods for more efficient conformational sampling, accuracy of the physical models used, and theoretical approaches to integrate experiments and simulations. These developments are enabling detailed studies of complex biomolecular assemblies.
The simulator is an R package that streamlines the process of performing simulations by creating a common infrastructure that can be easily used and reused across projects. Methodological statisticians routinely write simulations to compare their methods to preexisting ones. While developing ideas, there is a temptation to write "quick and dirty" simulations to try out ideas. This approach of rapid prototyping is useful but can sometimes backfire if bugs are introduced. Using the simulator allows one to remove the "dirty" without sacrificing the "quick." Coding is quick because the statistician focuses exclusively on those aspects of the simulation that are specific to the particular paper being written. Code written with the simulator is succinct, highly readable, and easily shared with others. The modular nature of simulations written with the simulator promotes code reusability, which saves time and facilitates reproducibility. The syntax of the simulator leads to simulation code that is easily human-readable. Other benefits of using the simulator include the ability to "step in" to a simulation and change one aspect without having to rerun the entire simulation from scratch, the straightforward integration of parallel computing into simulations, and the ability to rapidly generate plots, tables, and reports with minimal effort.
Researchers seek to understand our Universe by making model predictions to match observations. Historically, they have been able to model simple or highly simplified physical systems, jokingly dubbed the "spherical cows," with pencils and paper. Later, the arrival of computers enabled them to model complex phenomena with numerical simulations. For example, researchers have programmed supercomputers to simulate the motion of billions of particles through billions of years of cosmic time, a procedure known as the N-body simulations, in order to study how the Universe evolved to what we observe today. "Now with machine learning, we have developed the first neural network model of the Universe, and demonstrated there's a third route to making predictions, one that combines the merits of both analytic calculation and numerical simulation," said Yin Li, a Postdoctoral Researcher at the Kavli Institute for the Physics and Mathematics of the Universe, University of Tokyo, and jointly the University of California, Berkeley.