Molecular dynamics techniques in the studies of the bacterial ribosome

We summarize here the recent applications of molecular dynamics (MD) and enhanced sampling methods used to elucidate the role of flexibility in ribosome functioning. In the last decade, many atomic resolution structures of the bacterial ribosome have been solved, which allowed for extensive all-atom MD studies of this system. However, the time scale of such simulations is often not sufficient due to the large number of atoms building the ribosome complex. One of the ways to overcome this problem are enhanced sampling techniques. For instance, steered MD gave us knowledge about the dynamics of nascent peptide chain in the ribosomal exit tunnel. Targeted MD was used to study pathways of tRNA accommodation into the ribosome. Other MD-based techniques (MDFF and MDfit) allowed for generation of full-atom models from mediumresolution cryo-electron microscopy (cryo-EM) maps. Also, the studies on models of ribosomal aminoacyl-tRNA binding site (A-site) improved our understanding of the mRNA decoding process. For example, replica exchange molecular dynamics (REMD) was used to study the movement of the two key adenines, involved in the mRNA decoding process. The REMD extensive sampling allowed for construction of free energy landscapes. In summary, the MD-based techniques are very helpful in expanding our knowledge of the ribosome functioning and they successfully complement the experimental studies.