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projects:tauramddescription [2020/07/21 08:33]
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projects:tauramddescription [2020/09/28 16:47] (current)
kokhadmin [RAMD and its applications (using the implementation in Gromacs) are described in:]
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-<​html><​h2>​RAMD and its applications (using the implementation in NAMD) are described in:</h2>+=====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]]
  
  
-<​ul><​li>​Kokh DB et. al.&​nbsp;​Estimation of Drug-Target Residence Times by τ-Random Acceleration Molecular Dynamics Simulations.&​nbsp;<​em>​J. Chem. Theory Comput.</​em>​2018;&​nbsp;<​a href="​https://​pubs.acs.org/​doi/​10.1021/​acs.jctc.8b00230"​ target="​_blank"​ rel="​noreferrer noopener">​DOI:​ 10.1021/​acs.jctc.8b00230</​a></​li><​li>​Niu,​ Y.,&​nbsp;​Li,​ S.,&​nbsp;​Pan,​ D.,&​nbsp;​Liu,​ H.,&​nbsp;​Yao,​ X.&​nbsp;​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.&​nbsp;<​em>​Phys. Chem. Chem. Phys.</​em>&​nbsp;​2016,&​nbsp;<​em>​18</​em>&​nbsp;​(7),​5622–&​nbsp;​5629,&​nbsp;<​a href="​http://​pubs.rsc.org/​en/​content/​articlelanding/​2016/​cp/​c5cp06257h#​!divAbstract"​ target="​_blank"​ rel="​noreferrer noopener">​DOI:​ 10.1039/​C5CP06257H</​a></​li><​li>​Xiaofeng Yu, Prajwal Nandekar, Ghulam Mustafa, Vlad Cojocaru, Galina I. Lepesheva and Rebecca C. Wade.&​nbsp;​Ligand tunnels in T. brucei and human CYP51: Insights for parasite-specific drug design. Biochim. Biophys. Acta (BBA) – General Subjects , (2016) 1860:​67-78,&​nbsp;<​a href="​https://​www.ncbi.nlm.nih.gov/​pmc/​articles/​PMC4689311/"​ target="​_blank"​ rel="​noreferrer noopener">​DOI:​ 10.1016/​j.bbagen.2015.10.015</​a></​li><​li>​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,&​nbsp;<​a href="​http://​www.eurekaselect.com/​75602/​article"​ target="​_blank"​ rel="​noreferrer noopener">​DOI:​ 10.2174/​138920012798918462</​a></​li><​li>​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).<​a href="​http://​dx.doi.org/​10.1529/​biophysj.108.139675">​DOI:​10.1529/​biophysj.108.139675</​a></​li></​ul>​+=====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.]]
  
-<h2>RAMD and its applications ​(using ​the implementation in AMBER unless otherwise specified) are described in:</h2>+=== 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]]
  
- 
-<​ul><​li>​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.&​nbsp;<​a href="​https://​link.springer.com/​article/​10.1007%2Fs008940050053"​ target="​_blank"​ rel="​noreferrer noopener">​DOI:​10.1007/​s008940050053</​a>&​nbsp;​(Initial ARGOS implementation)</​li><​li>​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).&​nbsp;<​a href="​http://​dx.doi.org/​10.1006/​jmbi.2000.4154">​doi:​10.1002/​jmbi.2000.4154</​a>&​nbsp;​(First description of method and implementation in ARGOS)</​li><​li>​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).&​nbsp;<​a href="​http://​www.ijc.com/​articles/​2001v4/​6/">​http://​www.ijc.com/​articles/​2001v4/​6/</​a>&​nbsp;​(using the ARGOS implementation)</​li><​li>​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).&​nbsp;<​a href="​http://​www.pnas.org/​cgi/​content/​full/​99/​8/​5361">​Full text</​a>&​nbsp;​(using the ARGOS implementation)</​li><​li>​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).<​a href="​http://​dx.doi.org/​10.1038/​sj.embor.7400420">​doi:​10.1038/​sj.embor.7400420</​a></​li><​li>​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).<​a href="​http://​dx.doi.org/​10.1529/​biophysj.106.082917">​doi:​10.1529/​biophysj.106.082917</​a>&​nbsp;​(Implementation in CHARMM)</​li><​li>​Wang,​ T., Duan, Y. Chromophore channeling in the G-protein coupled receptor rhodopsin.&​nbsp;​J. Am. Chem. Soc. 129, 6970-6971 (2007).<​a href="​http://​dx.doi.org/​10.1021/​ja0691977">​doi:​10.1021/​ja0691977</​a></​li><​li>​Long,​ D., Mu, Y. Yang, D. Molecular Dynamics Simulation of Ligand Dissociation from Liver Fatty Acid Binding Protein. PLoS ONE 4, e6801 (2008).<​a href="​http://​dx.doi.org/​10.1371/​journal.pone.0006081">​doi:​10.1371/​journal.pone.0006081</​a>&​nbsp;​(Implementation of a variant of RAMD in GROMACS)</​li><​li>​Perakyla,​ M. Ligand unbinding pathways from the vitamin D receptor studied by molecular dynamics simulations. 38, 185-198 (2009).<​a href="​http://​dx.doi.org/​10.1007/​s00249-008-0369-x">​doi:​10.1007/​s00249-008-0369-x</​a></​li><​li>​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).<​a href="​http://​dx.doi.org/​10.1016/​j.jmb.2009.06.076">​doi:​10.1016/​j.jmb.2009.06.076</​a></​li><​li>​Pavlova,​ M. et al. Redesigning dehalogenase access tunnels as a strategy for degrading an anthropogenic substrate Nature Chem. Biol. 5, 727-733 (2009).<​a href="​http://​dx.doi.org/​10.1038/​nchembio.205">​doi:​10.1038/​nchembio.205</​a></​li><​li>​Wang,​ T., Duan, Y. Ligand entry and exit pathways in the beta2-adrenergic receptor. J. Mol. Biol. 392, 1102-1115 (2009).<​a href="​http://​dx.doi.org/​10.1016/​j.jmb.2009.07.093">​doi:​10.1016/​j.jmb.2009.07.093</​a></​li></​ul>​ 
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- 
- 
-<​h2>​Tutorial on application of RAMD</​h2>​ 
- 
- 
- 
-<p>A tutorial describing the&​nbsp;<​a href="​https://​www.h-its.org/​downloads/​ramd/"​ target="​_blank"​ rel="​noreferrer noopener">​τRAMD</​a>&​nbsp;​process of setting up and running RAMD simulations in NAMD for estimation of the relative residence time (τ) of a protein-small molecule complex can be found&​nbsp;<​a href="​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/"​ target="​_blank"​ rel="​noreferrer noopener">​here.</​a></​p>​ 
-<p>A tutorial describing the&​nbsp;<​a href="​https://​github.com/​HITS-MCM/​gromacs-ramd"​ target="​_blank"​ rel="​noreferrer noopener">​τRAMD</​a>&​nbsp;​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&​nbsp;<​a href="​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/"​ target="​_blank"​ rel="​noreferrer noopener">​here.</​a></​p>​ 
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-  </​div>​ 
-                  ​ 
-<div class="​software-preview">​ 
-  <​h3>​τRAMD</​h3>​ 
-  ​ 
-<​p>​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.</​p>​ 
-      <a href="​https://​www.h-its.org/​downloads/​ramd/">​Read more</​a>​ 
-  </​div>​ 
-</​html>​ 
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