Random Acceleration Molecular Dynamics (RAMD)

RAMD is used to identify ligand exit routes from the buried binding pockets of receptors and investigate the mechanism of ligand dissociation. In RAMD method, to accelerate the exit of a ligand from the binding pocket of its receptor, a force (F) of random orientation is applied on the center of mass of the ligand for N simulation steps. The movement of the ligand is assessed after these N simulation steps by calculating the distance r between the new and the old positions of its center of mass. If the change in distance r is less than the threshold distance r_min, a new random direction of the force is generated. If r is greater than r_min, the simulation is continued for the next N simulation steps with the same direction of the force.

Software and instructions for running RAMD can be found :

1. for  NAMD MD package here
2. for Gromacs MD package here.
3. for AMBER MD package here

RAMD is used in the tauRAMD protocol for computing relative protein-ligand residence times. RAMD can also be used to identify and define ligand pathways or collective variables which are then sampled more extensively with another technique, e.g. steered MD or umbrella sampling.
 

References:

1. Lüdemann SK, Carugo O, Wade RC. Substrate Access to Cytochrome P450cam: A Comparison of a Thermal Motion Pathway Analysis with Molecular Dynamics Simulation Data. Mol Model Annu. 1997; 3: 369–374.

2. Lüdemann SK, Lounnas V, Wade RC. How do substrates enter and products exit the buried active site of cytochrome P450cam? Random expulsion molecular dynamics investigation of ligand access channels and mechanisms. J Mol Biol. Elsevier; 2000; 303: 797–811.

2. Kokh DB et. al.  A workflow for exploring ligand dissociation from a macromolecule: Efficient random acceleration molecular dynamics simulation and interaction fingerprint analysis of ligand trajectories, J. Chem. Phys. 153, 125102 (2020); DOI: 10.1063/5.0019088