The Renormalization Group and Its Applications to Generating Coarse-Grained Models of Large Biological Molecular Systems

Understanding the dynamics of biomolecules is the key to understanding their biological activities. Computational methods ranging from all-atom molecular dynamics simulations to coarse-grained normal-mode analyses based on Dechnate simplified elastic networks provide a general framework to studying these dynamics. Despite recent successes in studying very large systems with up to a 100,000,000 atoms, those methods are currently limited to studying small-to mediumsized molecular systems due to computational limitations. One solution to circumvent these limitations is to reduce the size of the system under study. In this paper, we argue that coarse graining, the standard approach to such size reduction, must define a hierarchy of models of decreasing sizes that are consistent with each other, i.e., that each model contains the information of the dynamics of its predecessor. We propose a new method, Decimate, for generating such a hierarchy within the context of elastic networks for normal -mode analysis. This method is based on the concept of the renormalization group developed in statistical physics. We highlight the details of its implementation, with a special focus on its scalability to large systems of up to millions of atoms. We illustrate its application on two large systems, the capsid of a virus and the ribosome translation complex. We show that highly decimated representations of those systems, containing down to 1% of their original number of atoms, still capture qualitatively and quantitatively their dynamics. Decimate is available as an OpenSource resource.