The "lib/ramd" directory stores the tcl scripts and the example files for the implementation of the Random Acceleration Molecular Dynamics (RAMD) simulation method in NAMD. The RAMD method can be used to carry out molecular dynamics (MD) simulations with an additional randomly oriented acceleration applied to the center of mass of one group of atoms (referred below as "ligand") in the system. It can, for example, be used to identify egress routes for a ligand from a buried protein binding site. Since its original implementation in the ARGOS (ref 1, 2) program, the method has been also implemented in AMBER 8 (ref 3), and CHARMM (ref 4). The first implementation of RAMD in NAMD using a tcl script (available as supplementary material in ref 6) provided only limited functionality compared to the AMBER 8 implementation.
In the current implementation, the RAMD method can be performed in 2 flavors: (i) "pure RAMD simulations" in which the randomly-oriented acceleration is applied continuously, and (ii) "combined RAMD-MD simulations" in which RAMD steps alternate with standard MD steps. Additional information is found in the README file in the "lib/ramd" directory. The user is encouraged to carefully read this information before starting production runs.
The three required scripts are stored in "lib/ramd/scripts": (i) ramd-4.0.tcl defines the simulation parameters and passes them from the NAMD configuration file to the main script, (ii) "ramd-4.0_script.tcl" adds the randomly oriented force and performs all related computations, and (iii) "vectors.tcl" was borrowed from VMD and defines the vector operations used.
Two examples for running the scripts are included in the directory "lib/ramd/examples". The user is encouraged to read the "README.examples" file provided in the same directory.
In order to turn RAMD on, the line "source /path/to/your/files/ramd-4.0.tcl" should be included in the NAMD configuration file. Unless the user decides to store the scripts at a different location, the path "/path/to/your/files" should point to the "lib/ramd/scripts" directory. Otherwise, the user should make sure that the directory "/path/to/your/files" stores all three scripts described above.
The specific RAMD simulation parameters to be provided in the NAMD configuration file (listed below) should be preceded by the keyword "ramd". The default values for these parameters are only given as guidance. They are likely not to be suitable for other systems than those the scripts were tested on.
Start RAMD-MD with MD or RAMD?
Acceptable Values: yes or no
Default Value: no
Description: Specifies if combined RAMD-MD simulation starts with MD or RAMD steps; ignored if pure RAMD simulation is performed. Should be set to "yes" if initial MD steps are desired.
Note: In combined RAMD-MD simulations, RAMD blocks alternate with standard MD blocks ('ramdSteps' and 'mdSteps' input parameters). The switches between RAMD and MD blocks are decided based on the following parameters: (i) 'd' = the distance between the protein and ligand centers of mass, (ii) 'dr' = the distance traveled by the ligand in 1 RAMD block, and (iii) 'dm' = the distance traveled by the ligand in 1 MD block. A switch from RAMD to MD is applied if 'dr' 'rRamdMin'. A switch from MD to RAMD is applied if: (i) 'dm' 'rMdMin' and 'd' 0 (acceleration direction is kept from previous RAMD block), (ii) if 'dm' 'rMdMin' and 'd' 0 (acceleration direction is changed), (iii) if 'dm' 'rMdMin' and 'd' 0 (acceleration direction is changed). In all other case, a switch is not applied.