Systematically Defining Coarse-Grained Representations of Large Biomolecular Complexes

Abstract

Various biomolecular complexes are involved in many important biological processes. For example, the ribosome is a very large RNA-protein assembly that plays a central role in protein biosynthesis. Microtubules serve as a structural component of the cytoskeleton. It would be difficult to use large-scale atomistic molecular dynamics (MD) simulations to study the functional motions of these systems because of computational expense, and furthermore, high resolution atomic structures for such complexes may not even be available. Therefore various coarse-grained (CG) approaches have attracted rapidly growing interest, which enable simulations of large biomolecular complexes over longer effective timescales than MD simulations. We have developed a novel and systematic method for constructing CG representations of arbitrarily complex biomolecules, in order to preserve the large-scale and functionally relevant essential dynamics (ED) at the CG level. In the ED-CG scheme, the essential dynamics can be captured from principal component analysis (PCA) of a MD trajectory, elastic network model (ENM) of a single atomic structure, or a low-resolution cryo-electron microscopy density map. The method has been applied to the E. coli. ribosome and a microtubule to characterize CG models with different resolutions. The results illustrate that functionally important essential dynamics can still be captured even with aggressive coarse-graining.