Speaker
Dr
Michael Martinez
(Heidelberg Institute for Theoretical Studies)
Description
Studies of macromolecular interactions in solution are
important for understanding biological activities such as
protein-protein interactions in the regulation of signaling
pathways. Brownian dynamics simulations are well adapted to
the computation of kinetic rates of association between two
or more macromolecules (often proteins). Furthermore they
have been successfully used to perform protein-protein
docking and to study protein-surface interactions and
crowded macromolecular environments. However, Brownian
dynamics simulations are often limited by the representation
of macromolecules as rigid bodies.
We have addressed this limitation by extending the SDA6
(Simulation of Diffusional Association [Gabdouline, Wade,
1997]) software to incorporate flexibility of interacting
macromolecules. The software incorporates features from the
original SDA6 software as well as the SDAMM (SDAMM
[Mereghetti, Gabdouline, Wade, 2010] ) software designed to
study crowded macromolecular environments. The new software,
SDAFlex, has been written using an object-oriented approach,
uses less memory and can be run in parallel on shared-memory
architecture hardware.
SDAFlex simulates flexibility by switching between
predefined macromolecular conformations determined by normal
mode analysis, NMR or molecular dynamics. Two schemes for
accepting conformational switches are implemented: the first
which minimises the total system energy; the second a
Monte-Carlo algorithm. SDAFlex enables fast generation of
docking poses using multiple-conformations and calculation
of kinetic rates of association when flexibility and/or a
crowded environments are accounted for.