Mechanochemical Modeling of DNA Translocases

Joshua Adelman, University of California, Berkeley

RecA-like motor proteins comprise a large class of multimeric enzymes that convert chemical energy from ATP into mechanical work. Here we investigate dsDNA translocases, FTSK and the j29 viral packaging motor, belonging to this family. We develop a generalized framework for course-graining these proteins that allows us to make a direct connection between the spatial and chemical dynamics of the protein, while considering coordination between subunits. We model the major conformational motions of the protein along set of collective coordinates, while the mechanical forces driving the system are captured by a set of potential energy functions defined for each chemical state. We infer the potential energy landscape from the molecular structures, which are further refined by biochemical and biophysical measurements. The dynamics of the proteins are then studied by solving the continuous governing equations, which consist of Langevin or Fokker-Planck equations along the spatial coordinates and Markov jumps between the potentials. The framework is then used to investigate mechanochemical models of the protein.

Abstract Author(s): Joshua L. Adelman, Andrew Spakowitz, Jianhua Xing, George Oster