Protein synthesis by the ribosome requires large-scale rearrangements of the ‘small’ subunit (SSU; ∼1 MDa), including inter- and intra-subunit rotational motions. However, with nearly 2000 structures of ribosomes and ribosomal subunits now publicly available, it is exceedingly difficult to design experiments based on analysis of all known rotation states. To overcome this, we developed an approach where the orientation of each SSU head and body is described in terms of three angular coordinates (rotation, tilt and tilt direction) and a single translation. By considering the entire RCSB PDB database, we describe 1208 fully-assembled ribosome complexes and 334 isolated small subunits, which span >50 species. This reveals aspects of subunit rearrangements that are universal, and others that are organism/domain-specific. For example, we show that tilt-like rearrangements of the SSU body (i.e. ‘rolling’) are pervasive in both prokaryotic and eukaryotic (cytosolic and mitochondrial) ribosomes. As another example, domain orientations associated with frameshifting in bacteria are similar to those found in eukaryotic ribosomes. Together, this study establishes a common foundation with which structural, simulation, single-molecule and biochemical efforts can more precisely interrogate the dynamics of this prototypical molecular machine.

Applying simulations with structure-based Go À like ð Þmodels has proven to be an effective strategy for investigating the factors that control biomolecular dynamics. The common element of these models is that some (or all) of the intra/inter-molecular interactions are explicitly defined to stabilize an experimentally determined structure. To facilitate the development and application of this broad class of models, we previously released the SMOG 2 software package. This suite allows one to easily customize and distribute structurebased (i.e., SMOG) models for any type of polymer-ligand system. The force fields generated by SMOG 2 may then be used to perform simulations in highly optimized MD packages, such as Gromacs, NAMD, LAMMPS, and OpenMM.Here, we describe extensions to the software and demonstrate the capabilities of the most recent version (SMOG v2.4.2). Changes include new tools that aid user-defined customization of force fields, as well as an interface with the OpenMM simulation libraries (OpenSMOG v1.1.0). The OpenSMOG module allows for arbitrary user-defined contact potentials and non-bonded potentials to be employed in SMOG models, without source-code modifications. To illustrate the utility of these advances, we present applications to systems with millions of atoms, long polymers and explicit ions, as well as models that include non-structure-based (e.g., AMBER-based) energetic terms. Examples include Antonio B. de Oliveira Jr and Vinícius G. Contessoto contributed equally to this work.