Methods for refining interactively established models of ribosomal RNA towards a physico‐chemically plausible structure

A computational multiscale modeling approach that was used for the refinement of the structure of the bacterial ribosome is presented. Though designed for the ribosome, the methods are applicable to other large biomolecules as well. Algorithms were developed, allowing defined groups of atoms to be clustered into rigid objects, which greatly reduces the number of parameters in the molecular dynamics approach and thus speeds up the computational process considerably (clustered molecular dynamics). The energy potential function, which is used in molecular dynamics to describe structural details of a particle, was extended to include terms that describe high‐level biochemical constraints resulting from crosslinking techniques and cryo‐electron microscopy. High‐ and low‐level features of the potential function were specified, and the clustered molecular dynamics technique was integrated into the interactive model‐building process, to establish a physico‐chemically plausible structure of the bacterial ribosomal RNA. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 407–417, 2001