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 to 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 [59,109] program, the method has been implemented in AMBER 8 , and CHARMM . The first implementation of RAMD in NAMD using a tcl script (available as supplementary material in ) provided only limited functionality compared to the AMBER 8 implementation and was followed with an implementation of RAMD and RAMD-MD in NAMD [24,9]. Recently the RAMD method was improved in speed by using NAMD vector implementations and streamlining the code. The current implementation is now focused on the RAMD simulation and was used in the RAMD procedure for the estimation of relative drug-target residence times .
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 two required scripts are stored in ``lib/ramd/scripts": (i) ramd-5.tcl defines the simulation parameters and passes them from the NAMD configuration file to the main script, (ii) ``ramd-5_script.tcl" adds the randomly oriented force and performs all related computations.
Two examples for running RAMD are included in the directory ``lib/ramd/example/". The examples can be started using the RAMD-force.sh shell scripts.
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 may not to be suitable for other systems.
Mandatory parameter settings:
Optional parameter settings with a default. Depending on your simulation system, you might want to change these settings:
Note: In the current RAMD implementation, combined RAMD-MD simulations, where RAMD blocks alternate with standard MD blocks are not available. In case you are are interested in this feature, please contact the RAMD developers at firstname.lastname@example.org
Scripts for using RAMD in the RAMD procedure for computing residence times are available at: https://www.h-its.org/downloads/ramd/.