- installation and compilation
- how to get started
- how to run SDA 7
- description of input files
- description of output files
- description of the Effective Charges Model
- description of the tools
- documentation for developers
SDA7 can be used to carry out Brownian dynamics simulations of the diffusional association in a continuum aqueous solvent of two solute molecules, e.g. proteins, or of a solute molecule to an inorganic surface. SDA7 can also be used to simulate the diffusion of multiple proteins, in dilute or concentrated solutions, e.g., to study the effects of macromolecular crowding.
If the 3D structure of the bound complex is unknown, SDA can be used for rigid-body docking to predict the structure of the diffusional encounter complex or the orientation in which a protein binds to a surface. The configurations obtained from SDA can subsequently be refined by running molecular dynamics simulations to obtain structures for fully bound complexes.
If the 3D structure of the bound complex is known, SDA can be used to calculate bimolecular association rate constants. It can also be used to record Brownian dynamics trajectories or encounter complexes and to calculate bimolecular electron transfer rate constants.
While these Brownian dynamics simulations are usually carried out with rigid solutes, in SDA7 we give a possibility to assign more than one conformation to each solute molecule. This allows some large-scale internal dynamics of macromolecules to be considered in the simulations.
In this SDA distribution, there is a single executable, sda_flex, which will execute different types of simulation:
- Compute the bimolecular diffusional association rate constant for 2 solutes using a user-defined set of intermolecular contact distances as reaction criteria (see the example here)
- Compute the rate constants for electron transfer from the relative diffusion of two proteins (see the example here)
- Perform rigid-body docking of two macromolecules (see the example here)
- Perform rigid-body docking of a solute and a surface (see the example here)
- Calculate the time during which user-defined contacts are maintained; this gives an approximation for the lifetimes of a complex. The starting configurations may be from a crystal structure or recorded from a simulation (see the example here)
- Re-calculate energies for a recorded set of configurations (see the example here)
- Compute PMFs for protein/surface binding (see the example here)
- Perform simulations of the diffusion of multiple proteins (see the adsorption process of HEWL to a mica-like surface, example for rigid molecules, flexible molecules, or rigid molecules and a solid surface)
The simulations can be run in serial or in parallel mode on a shared-memory computer architecture.
Note that the example cases have parameter settings to allow results to be obtained in rather short calculation times. For real applications, parameter settings will need to be changed and all input parameters, which are described here, should be checked carefully.
In addition, there are various auxiliary programs for the preparation of input data and for the analysis of the output results (see the description of the tools).webSDA provides a good starting point for gaining familiarity with the workflow for performing calculations with SDA. The general procedure for running an SDA calculation is described in how to run SDA 7. The examples provide starting points for all the calculation types and the tutorial provides more detailed (although not completely up-to-date) stepwise guidance through calculations with SDA.
- ECM - Effective Charges for Macromolecules in solvent - a program to calculate effective charges used for computing electrostatic interaction forces and energies. It is included in this SDA distribution.
- Adaptive Poisson-Boltzmann Solver used by SDA to calculate electrostatic potentials. (APBS calculated electrostatic potentials should be converted to binary UHBD format.)
UHBD - University of Houston Brownian Dynamics program used by SDA to calculate electrostatic potentials.
- VMD with the Pathways plugin. - to calculate the electronic coupling between donor (or acceptor) atoms and accessible atoms of a protein (for electron transfer rate calculations only).
- NACCESS - solvent accessible surface area calculation program. By default, the SDA 7 distribution provides a different implementation for solvent accessible surface area calculations but the code can be compiled to use NACCESS instead (e.g. for very large systems).