Going Big: Million Atom Simulations of Ribosomes and Billion Atom Simulations of Chromatin

Abstract

The rapid increase of computing power has enabled atomistic simulations of larger and larger systems. High performance computing (HPC) platforms with more than one million processor cores are not uncommon among the world's fastest supercomputers. Efficient utilization of these machines requires careful attention to parallel decomposition of the problem. Explicit solvent molecular dynamics (MD) simulations of large macromolecular complexes play an important role in integrating disparate forms of experimental data into a single coherent picture. These simulations help set the stage for reduced model and coarse-grained (CG) simulations capable of simulating large-scale conformational changes important for mechanistic understanding. We used explicit solvent MD simulations to identify the accommodation corridor in the ribosome, critical for tRNA selection during protein synthesis (Sanbonmatsu, et al., PNAS, 2005). Microsecond explicit solvent simulations of the ribosome (2.2 million atoms) also laid the foundations for our energy landscape calculations using all-atom structure-based simulations of spontaneous accommodation events (Whitford, et al., PLoS Comput. Biol., 2013; Whitford, et al., RNA, 2010). We are applying a similar strategy to chromatin architecture, which plays a key role in embryo development, brain function and cancer. As a first step, we have performed the first explicit solvent simulation of an entire gene locus (GATA4), consisting of 427 nucleosomes and over one billion atoms (the first published billion atom biomolecular simulation) (Jung, et al., J. Comp. Chem. 2019). Simulations used the GENESIS molecular dynamics code on the LANL Trinity supercomputer. The multi-disciplinary effort combined computer science, high performance computing, chip design, biophysics, structural biology, and cell biology, including researchers from RIKEN, LANL, NYU, Intel and Cray. Several performance optimizations for the KNL architecture enabled scaling to large numbers of cores.