Brownian dynamics simulations of biomolecular diffusional association processes

Advanced Review:

Brownian dynamics (BD) is a computational method to simulate molecular diffusion
processes. Although the BD method has been developed over several
decades and is well established, new methodological developments are improving
its accuracy, widening its scope, and increasing its application. In biological
applications, BD is used to investigate the diffusive behavior of molecules subject
to forces due to intermolecular interactions or interactions with material surfaces.
BD can be used to compute rate constants for diffusional association, generate
structures of encounter complexes for molecular binding partners, and
examine the transport properties of geometrically complex molecules. Often, a
series of simulations is performed, for example, for different protein mutants or
environmental conditions, so that the effects of the changes on diffusional properties
can be estimated. While biomolecules are commonly described at atomic
resolution and internal molecular motions are typically neglected, coarsegraining
and the treatment of conformational flexibility are increasingly
employed. Software packages for BD simulations of biomolecules are growing in
capabilities, with several new packages providing novel features that expand the
range of questions that can be addressed. These advances, when used in concert
with experiment or other simulation methods, such as molecular dynamics,
open new opportunities for application to biochemical and biological systems.
Here, we review some of the latest developments in the theory, methods, software,
and applications of BD simulations to study biomolecular diffusional association
processes and provide a perspective on their future use and application
to outstanding challenges in biology, bioengineering, and biomedicine.