=====References=====
====RAMD and its applications (using the implementation in Gromacs) are described in:====
  * Kokh DB et. al. A Workflow for Exploring Ligand Dissociation from a Macromolecule: Efficient Random Acceleration Molecular Dynamics Simulation and Interaction Fingerprints Analysis of Ligand Trajectories. J. Chem. Phys. 153, 125102 (2020); https://doi.org/10.1063/5.0019088 or **arXiv** 2020 [[https://arxiv.org/abs/2006.11066|arXiv:2006.11066]] 
====RAMD and its applications (using the implementation in NAMD) are described in:====
  * Kokh DB et. al. Machine Learning Analysis of τRAMD Trajectories to Decipher Molecular Determinants of Drug-Target Residence Times. Front. Mol. Biosci. 2019 [[https://www.frontiersin.org/articles/10.3389/fmolb.2019.00036/full|DOI: 10.1021/acs.jctc.8b00230]] 
  * Kokh DB et. al. Estimation of Drug-Target Residence Times by τ-Random Acceleration Molecular Dynamics Simulations. J. Chem. Theory Comput. 2018, **14**, 7, 3859–3869 2018 [[https://pubs.acs.org/doi/abs/10.1021/acs.jctc.8b00230|DOI: 10.1021/acs.jctc.8b00230]] 
  * Niu, Y., Li, S., Pan, D., Liu, H., Yao, X. Computational Study on the Unbinding Pathways of B-RAF Inhibitors and Its Implication for the Difference of Residence Time: Insight from Random Acceleration and Steered Molecular Dynamics Simulations. Phys. Chem. Chem. Phys. 2016, **18** (7),5622–5629, [[http://pubs.rsc.org/en/content/articlelanding/2016/cp/c5cp06257h#!divAbstract|DOI: 10.1039/C5CP06257H]]
  * Xiaofeng Yu, Prajwal Nandekar, Ghulam Mustafa, Vlad Cojocaru, Galina I. Lepesheva and Rebecca C. Wade. Ligand tunnels in T. brucei and human CYP51: Insights for parasite-specific drug design. Biochim. Biophys. Acta (BBA) – General Subjects, (2016) 1860:67-78, [[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4689311/|DOI: 10.1016/j.bbagen.2015.10.015]]
  * Vlad Cojocaru, Peter J. Winn and Rebecca C. Wade, Multiple, Ligand-dependent Routes from the Active Site of Cytochrome P450 2C9. Curr. Drug. Metab. (2012) 13:143-154, [[http://www.eurekaselect.com/75602/article|DOI: 10.2174/138920012798918462]]
  * Vashisth, H., Abrams, C.F. Ligand escape pathways and (un)binding free energy calculations for the hexameric insulin-phenol complex. Biophys. J. 95, 4193-4204 (2008). [[http://dx.doi.org/10.1529/biophysj.108.139675|DOI:10.1529/biophysj.108.139675]]

====RAMD and its applications (using the implementation in AMBER unless otherwise specified) are described in====
  * Lüdemann SK, Carugo O, Wade RC. Substrate access to cytochrome P450cam: a comparison of a thermal motion pathway analysis with molecular dynamics simulation data. J. Mol. Model. (1997) 3, 369-374. [[https://link.springer.com/article/10.1007%2Fs008940050053|DOI:10.1007/s008940050053]] (Initial ARGOS implementation)
  * Luedemann, S.K., Lounnas, V. and R. C. Wade. How do Substrates Enter and Products Exit the Buried Active Site of Cytochrome P450cam ? 1. Random Expulsion Molecular Dynamics Investigation of Ligand Access Channels and Mechanisms. J Mol Biol, 303:797-811 (2000). [[http://dx.doi.org/10.1006/jmbi.2000.4154|doi:10.1002/jmbi.2000.4154]] (First description of method and implementation in ARGOS)
  * Luedemann, S.K., Gabdoulline,R.R., Lounnas, V. and R. C. Wade. Substrate access to cytochrome P450cam investigated by molecular dynamics simulations: An interactive look at the underlying mechanisms. Internet Journal of Chemistry, 4, 6 (2001). [[
http://www.ijc.com/articles/2001v4/6/|http://www.ijc.com/articles/2001v4/6/]] (using the ARGOS implementation)
  * Winn,P., Luedemann, S.K., Gauges,R., Lounnas, V. and R. C. Wade. Comparison of the dynamics of substrate access channels in three cytochrome P450s reveals different opening mechanisms and a new functional role for a buried arginine PNAS, 99, 5361-5366 (2002). [[http://www.pnas.org/cgi/content/full/99/8/5361|Full text]] (using the ARGOS implementation)
  * Schleinkofer, K., Sudarko, Winn,P., Luedemann, S.K. and R. C. Wade. Do mammalian cytochrome P450s show multiple ligand access pathways and ligand channelling? EMBO Reports, 6, 584-589 (2005). [[http://dx.doi.org/10.1038/sj.embor.7400420|doi:10.1038/sj.embor.7400420]]
  * Carlsson, P., Burendahl, S., Nilsson, L. Unbinding of retinoic acid from the retinoic acid receptor by random expulsion molecular dynamics. Biophys. J. 91, 3151-3161 (2006).[[http://dx.doi.org/10.1529/biophysj.106.082917|doi:10.1529/biophysj.106.082917]] (Implementation in CHARMM)
  * Wang, T., Duan, Y. Chromophore channeling in the G-protein coupled receptor rhodopsin J. Am. Chem. Soc. 129, 6970-6971 (2007).[[http://dx.doi.org/10.1021/ja0691977|doi:10.1021/ja0691977]]
  * Long, D., Mu, Y. Yang, D. Molecular Dynamics Simulation of Ligand Dissociation from Liver Fatty Acid Binding Protein. PLoS ONE 4, e6801 (2008).[[http://dx.doi.org/10.1371/journal.pone.0006081|doi:10.1371/journal.pone.0006081]] (Implementation of a variant of RAMD in GROMACS)
  * Perakyla, M. Ligand unbinding pathways from the vitamin D receptor studied by molecular dynamics simulations. 38, 185-198 (2009).[[http://dx.doi.org/10.1007/s00249-008-0369-x|doi:10.1007/s00249-008-0369-x]]
  * Klvana, M. et al. Pathways and Mechanisms for Product Release in the Engineered Haloalkane Dehalogenases Explored Using Classical and Random Acceleration Molecular Dynamics Simulations J. Mol. Biol. 392, 1339-1356 (2009). [[http://dx.doi.org/10.1016/j.jmb.2009.06.076|doi:10.1016/j.jmb.2009.06.076]]
  * Pavlova, M. et al. Redesigning dehalogenase access tunnels as a strategy for degrading an anthropogenic substrate Nature Chem. Biol. 5, 727-733 (2009). [[http://dx.doi.org/10.1038/nchembio.205|doi:10.1038/nchembio.205]]
  * Wang, T., Duan, Y. Ligand entry and exit pathways in the beta2-adrenergic receptor. J. Mol. Biol. 392, 1102-1115 (2009). [[http://dx.doi.org/10.1016/j.jmb.2009.07.093|doi:10.1016/j.jmb.2009.07.093]]


=====Tutorials on the application of RAMD=====


=== Implementation in NAMD ===
A tutorial describing the τRAMD process of setting up and running [[https://www.h-its.org/downloads/ramd/|RAMD]]  simulations in NAMD for estimation of the relative residence time (τ) of a protein-small molecule complex can be found [[https://kbbox.h-its.org/toolbox/tutorials/estimation-of-relative-residence-times-of-protein-ligand-complexes-using-random-acceleration-molecular-dynamics-ramd-implementation-in-namd/|here.]]

=== Implementation in GROMACS ===
A tutorial describing the τRAMD process of setting up and running RAMD simulations in GROMACS for estimation of the relative residence time (τ) of a protein-small molecule complex can be found [[https://kbbox.h-its.org/toolbox/tutorials/estimation-of-relative-residence-times-of-protein-ligand-complexes-using-random-acceleration-molecular-dynamics-ramd-implementation-in-gromacs/|here]].

                  
=== τRAMD ===
τ-random acceleration molecular dynamics (τRAMD) is a protocol based on the RAMD method for the ranking of drug candidates by their residence time and obtaining insights into ligand-target dissociation mechanism. An introduction to the method is given [[https://youtu.be/kCUyQtoo4cE|here]]