τ-RAMD

The τRAMD (τ-Random Acceleration Molecular Dynamics) technique makes use of RAMD simulations to compute relative residence times (or dissociation rates) of protein-ligand complexes. In the RAMD method, the egress of a small molecule from a target receptor is accelerated by the application of an adaptive randomly oriented force on the ligand. This enables ligand egress events to be observed in short, nanosecond timescale simulations without imposing any bias regarding the ligand egress route taken. Apart from the estimation of relative residence times, the τRAMD method can be used to investigate dissociation mechanisms and characterize transition states by analysing the RAMD trajectories with the MD-IFP (Molecular Dynamics - Interaction Fingerprint) tool. The combined use of τRAMD and MD-IFP may assist the early stages of drug discovery campaigns for the design of new molecules or ligand optimization.