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.
