Modeling macromolecular motions in the cell by Brownian dynamics simulations
Macromolecular motions and interactions in the cell are essential events in cellular life and occur on a variety of time scales. Processes like macromolecular diffusion and transport, many types of protein-protein interactions, and protein domain rearrangements occur on timescales of milliseconds and longer. These processes cannot be described by standard molecular dynamics (MD) simulation methods. Brownian dynamics (BD) simulation is one of the methods that permits simulation of macromolecular motions on the millisecond time scale while keeping atomic level accuracy in the representation of the molecules, albeit usually neglecting the internal dynamics of macromolecules. We have previously written SDA, a software suite for the Simulation of Diffusional Association (http://projects.villa-bosch.de/mcm/software/sda). This permits the simulation of the relative diffusional motion of two atomically detailed macromolecules to compute association rate constants and study encounter complex formation. The goal of this project is to develop this software and the methodology so that the diffusional motion of many macromolecules or large proteins consisting of rigid domains connected by flexible linkers can be simulated with a force field based on the atomically detailed protein structure.
