This example can be found in the directory examples/lysozymes/128_flex. The full list of directories in examples/lysozymes includes:
| prepare_grids_and_ecm/ | Directory to generate the data files (pdbs, grids and effective charges) into the data_grid/ directory |
| data_grid/ | Data files (pdb and input files) needed for running the examples |
| 128_ph6/ | Results of a SDAMM run where all lysozymes are at a constant protonation state (ph6) |
| 128_flex/ | Results of a SDAMM run where lysozymes can change protonation states (ph3, ph6 or ph9) |
| doc/ | This documentation |
| unit-test/ | For developers, regression tests for different combinations of interactions. The grids need be generated first |
This input will run a SDAMM-type simulation of 128 lysozyme molecules at concentration of 15 g/L in a simulation box of 460 Å^3,
with PBC (similarly to the 128_ph6/ example).
In this case, however, each lysozyme is capable of dynamically changing its protonation state, i.e., the "flexibility" here means
that the configuration can be switched between the provided grids that contain different protonation states.
This resembles a constant pH simulation, and is perhaps more realistic since in a natural environment exchange of a protein's hydrogen atoms
with water can occur.
The protonation states of lysozymes have been computed at 3 different pH conditions:
- at pH 3, the total charge of the protein is +13 e¯
- at pH 6, +8 e¯
- and at pH 9, +7 e¯ (the N-terminus is not charged in this case)
The interactions among the lysozymes are represented fully, i.e., include the electrostatic term, soft-core repulsion, electrostatic desolvation and non-polar desolvation.
Assure you have compiled all the executables and tools in sda_flex/bin/ first (refer to the compilation section).
Then go to the examples/lysozymes/128_flex directory and execute the run script:
cd 128_flex/
../../../bin/sda_flex sdamm_flex.in > my_out_128_flex
You might read README files to see how to perform the analysis of the trajectory.
We advise to perform calculations in a separate directory, so that the original output files cannot be overwritten.
This folder contains examples for the usage of tools:
- generate_init_pos: to generate an initial configuration of the solutes inside a box
For every protein, the percentage of the total simulation time spent in each configuration (protonation state), is printed in the output file.
The trajectories in these examples are very short, but if you pursue the simulation for 100 ns or more, you should observe a convergence of the
protonation state occupancy.
In this simple example, obviously the protonation state at pH 9 (i.e., when the protein carries the lowest charge), is the most favorable electrostatically.
Simulations of a system of lysozymes with three different protonation states are described in detail in: Martinez,M. et al. (2015). SDA 7: A Modular and Parallel Implementation of the Simulation of Diffusional Association Software. J. Comput. Chem., 36, 1631–45. doi:10.1002/jcc.23971. Please note that these simulations were run with different parameters from those used in the example. The example is a smaller system (128 proteins instead of 256 proteins) and different parameters are used for computing the interactions between proteins.