Introduction

An enhanced sampling method that uses an artificial randomly oriented force to expel a ligand from its binding site on a macromolecule.

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 rmin, a new random direction of the force is generated. If r is greater than rmin, the simulation is continued for the next N simulation steps with the same direction of the force.

Software and instructions for running RAMD and simulations in NAMD can be found here.

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.

Computational Tools

Random Acceleration Molecular Dynamics (RAMD) can be performed using the following software tools: