Modeling Macromolecular Machines Using Rigid-Cluster Networks

Abstract

Many macromolecules consist of domains which act more or less as rigid bodies during large conformational changes. These collective motions are thought to be strongly related with the functions of a system. This fact encourages us to model a biomolecular structure as a set of rigid clusters which are interconnected with distance constraints. In this way the intermediate conformations in an anharmonic pathway can be determined by the translational and rotational displacements of large clusters in such a way that steric constraints are observed. In this paper, we present a geometry-based interpolation technique called rigid-cluster interpolation. This is an extension of the coarse-grained elastic network interpolation (ENI) method that we previously developed to generate physically realistic pathways between two different conformations of a macromolecule. We present the derivation of the rigid-cluster model and apply it to various “macromolecular machines”. Simulation results show that this method generates sterically feasible pathways of large systems in a very short time. The computational cost of the interpolation does not scale heavily with the size of structures, but rather depends strongly on the number of rigid-clusters.