Re: [gmx-users] how to calculate kinetic constant?
Hi Chris, The activation energy is obtained from the PMF well depth. So that leaves two variables k and A. If we get K at say 5 temepratures, and plot ln(k) vs. 1/T, the intercept will give us A. From that, at the temperature of interest, we can back out k. I will dig up the paper I saw this in. It was a really long time ago though. On Sun, Oct 6, 2013 at 2:33 AM, Christopher Neale chris.ne...@mail.utoronto.ca wrote: Dear Rajat: I just checked the first two papers that you mentioned and they both get kinetics from standard equilibrium simulations. As for the Arrhenius law, with k, A, and the energy of activation (Ea) all unknown for each T, how do you obtain a unique solution for k given T ? Even if you assume that Ea is some function of the maximum of your PMF (which is not always true), I presume that you can only then get the relationship between k and A, not the absolute value of k, even with information from many temperatures. However, I've never worked on this directly. Can you provide a reference so that I can take a look? Thank you, Chris. -- original message -- Hi Chris, I have never done this and I may be missing something. But here is what I think. I have seen a few papers use the Arrhenius law, k=A*exp (-deltaG/kB*T)...-deltaG/kB*T can be obtained from the PMF...Now, if you do this for different temperatures, you can back out the activation energy and hence the rate constant. I would love to learn more about this. Any inputs will be welcome. Regards, On Sat, Oct 5, 2013 at 11:44 PM, Christopher Neale chris.neale at mail.utoronto.ca wrote: If you want K_on and K_off, then I think you need to look at long-time equilibrium simulations or massively repeated simulations connected with a MSM. Beyond that, I believe that you will need to understand all of the important free energy barriers in all degrees of freedom (hard, to say the least). Rajat: how are you going to compute kinetics from a PMF? Barriers in orthogonal degrees of freedom don't show up on your PMF but can greatly affect the kinetics. Even relatively minor roughness of the multidimensional free energy surface and off-pathway kinetic traps are going to affect the kinetics but not the PMF. Some people have tried to circumvent this limitation by using the PMF in addition to computing the local diffusion at each small section of the order parameter (e.g., http://www.nature.com/nnano/journal/v3/n6/full/nnano.2008.130.html ) but unless there is excellent sampling overlap and lots of transitions between all relevant states, I see this as a way to calculate an upper bound of rates that I think could easily be much slower. See, for example, http://pubs.acs.org/doi/abs/10.1021/jp045544s . Finally, I am not sure how rates can be usefully extracted from a non-equilibrium method like REMD. Unless I missed it, the paper that David cites: http://pubs.acs.org/doi/abs/10.1021/ct400404q doesn't compute kinetics. Perhaps the OP can provide more information on what they are trying to obtain, exactly. Chris. -- original message -- If you are looking at binding/unbinding as a function of temperature (hopefully with REMD), you can use g_kinetics. If you are looking at unbinding/binding events in a single simulation with temperature, etc constant (no annealing), you will need to calculate binding probabilities, from which you can back out a rate constant. A simple google search gave me these papers (http://www.pnas.org/content/90/20/9547.full.pdf, http://pubs.acs.org/doi/abs/10.1021/jp037422q) Of course, the best approach is to calculate the PMF and back out the rate constant from the free energy. Hope that helps. -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! * Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists -- Rajat Desikan (Ph.D Scholar) Prof. K. Ganapathy Ayappa's Lab (no 13), Dept. of Chemical Engineering, Indian Institute of Science, Bangalore -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! * Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
[gmx-users] how to calculate kinetic constant?
If you want K_on and K_off, then I think you need to look at long-time equilibrium simulations or massively repeated simulations connected with a MSM. Beyond that, I believe that you will need to understand all of the important free energy barriers in all degrees of freedom (hard, to say the least). Rajat: how are you going to compute kinetics from a PMF? Barriers in orthogonal degrees of freedom don't show up on your PMF but can greatly affect the kinetics. Even relatively minor roughness of the multidimensional free energy surface and off-pathway kinetic traps are going to affect the kinetics but not the PMF. Some people have tried to circumvent this limitation by using the PMF in addition to computing the local diffusion at each small section of the order parameter (e.g., http://www.nature.com/nnano/journal/v3/n6/full/nnano.2008.130.html ) but unless there is excellent sampling overlap and lots of transitions between all relevant states, I see this as a way to calculate an upper bound of rates that I think could easily be much slower. See, for example, http://pubs.acs.org/doi/abs/10.1021/jp045544s . Finally, I am not sure how rates can be usefully extracted from a non-equilibrium method like REMD. Unless I missed it, the paper that David cites: http://pubs.acs.org/doi/abs/10.1021/ct400404q doesn't compute kinetics. Perhaps the OP can provide more information on what they are trying to obtain, exactly. Chris. -- original message -- If you are looking at binding/unbinding as a function of temperature (hopefully with REMD), you can use g_kinetics. If you are looking at unbinding/binding events in a single simulation with temperature, etc constant (no annealing), you will need to calculate binding probabilities, from which you can back out a rate constant. A simple google search gave me these papers (http://www.pnas.org/content/90/20/9547.full.pdf, http://pubs.acs.org/doi/abs/10.1021/jp037422q) Of course, the best approach is to calculate the PMF and back out the rate constant from the free energy. Hope that helps. -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! * Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
Re: [gmx-users] how to calculate kinetic constant?
Hi Chris, I have never done this and I may be missing something. But here is what I think. I have seen a few papers use the Arrhenius law, k=A*exp (-deltaG/kB*T)...-deltaG/kB*T can be obtained from the PMF...Now, if you do this for different temperatures, you can back out the activation energy and hence the rate constant. I would love to learn more about this. Any inputs will be welcome. Regards, On Sat, Oct 5, 2013 at 11:44 PM, Christopher Neale chris.ne...@mail.utoronto.ca wrote: If you want K_on and K_off, then I think you need to look at long-time equilibrium simulations or massively repeated simulations connected with a MSM. Beyond that, I believe that you will need to understand all of the important free energy barriers in all degrees of freedom (hard, to say the least). Rajat: how are you going to compute kinetics from a PMF? Barriers in orthogonal degrees of freedom don't show up on your PMF but can greatly affect the kinetics. Even relatively minor roughness of the multidimensional free energy surface and off-pathway kinetic traps are going to affect the kinetics but not the PMF. Some people have tried to circumvent this limitation by using the PMF in addition to computing the local diffusion at each small section of the order parameter (e.g., http://www.nature.com/nnano/journal/v3/n6/full/nnano.2008.130.html ) but unless there is excellent sampling overlap and lots of transitions between all relevant states, I see this as a way to calculate an upper bound of rates that I think could easily be much slower. See, for example, http://pubs.acs.org/doi/abs/10.1021/jp045544s . Finally, I am not sure how rates can be usefully extracted from a non-equilibrium method like REMD. Unless I missed it, the paper that David cites: http://pubs.acs.org/doi/abs/10.1021/ct400404q doesn't compute kinetics. Perhaps the OP can provide more information on what they are trying to obtain, exactly. Chris. -- original message -- If you are looking at binding/unbinding as a function of temperature (hopefully with REMD), you can use g_kinetics. If you are looking at unbinding/binding events in a single simulation with temperature, etc constant (no annealing), you will need to calculate binding probabilities, from which you can back out a rate constant. A simple google search gave me these papers (http://www.pnas.org/content/90/20/9547.full.pdf, http://pubs.acs.org/doi/abs/10.1021/jp037422q) Of course, the best approach is to calculate the PMF and back out the rate constant from the free energy. Hope that helps. -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! * Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists -- Rajat Desikan (Ph.D Scholar) Prof. K. Ganapathy Ayappa's Lab (no 13), Dept. of Chemical Engineering, Indian Institute of Science, Bangalore -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! * Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
[gmx-users] how to calculate kinetic constant?
Dear Rajat: I just checked the first two papers that you mentioned and they both get kinetics from standard equilibrium simulations. As for the Arrhenius law, with k, A, and the energy of activation (Ea) all unknown for each T, how do you obtain a unique solution for k given T ? Even if you assume that Ea is some function of the maximum of your PMF (which is not always true), I presume that you can only then get the relationship between k and A, not the absolute value of k, even with information from many temperatures. However, I've never worked on this directly. Can you provide a reference so that I can take a look? Thank you, Chris. -- original message -- Hi Chris, I have never done this and I may be missing something. But here is what I think. I have seen a few papers use the Arrhenius law, k=A*exp (-deltaG/kB*T)...-deltaG/kB*T can be obtained from the PMF...Now, if you do this for different temperatures, you can back out the activation energy and hence the rate constant. I would love to learn more about this. Any inputs will be welcome. Regards, On Sat, Oct 5, 2013 at 11:44 PM, Christopher Neale chris.neale at mail.utoronto.ca wrote: If you want K_on and K_off, then I think you need to look at long-time equilibrium simulations or massively repeated simulations connected with a MSM. Beyond that, I believe that you will need to understand all of the important free energy barriers in all degrees of freedom (hard, to say the least). Rajat: how are you going to compute kinetics from a PMF? Barriers in orthogonal degrees of freedom don't show up on your PMF but can greatly affect the kinetics. Even relatively minor roughness of the multidimensional free energy surface and off-pathway kinetic traps are going to affect the kinetics but not the PMF. Some people have tried to circumvent this limitation by using the PMF in addition to computing the local diffusion at each small section of the order parameter (e.g., http://www.nature.com/nnano/journal/v3/n6/full/nnano.2008.130.html ) but unless there is excellent sampling overlap and lots of transitions between all relevant states, I see this as a way to calculate an upper bound of rates that I think could easily be much slower. See, for example, http://pubs.acs.org/doi/abs/10.1021/jp045544s . Finally, I am not sure how rates can be usefully extracted from a non-equilibrium method like REMD. Unless I missed it, the paper that David cites: http://pubs.acs.org/doi/abs/10.1021/ct400404q doesn't compute kinetics. Perhaps the OP can provide more information on what they are trying to obtain, exactly. Chris. -- original message -- If you are looking at binding/unbinding as a function of temperature (hopefully with REMD), you can use g_kinetics. If you are looking at unbinding/binding events in a single simulation with temperature, etc constant (no annealing), you will need to calculate binding probabilities, from which you can back out a rate constant. A simple google search gave me these papers (http://www.pnas.org/content/90/20/9547.full.pdf, http://pubs.acs.org/doi/abs/10.1021/jp037422q) Of course, the best approach is to calculate the PMF and back out the rate constant from the free energy. Hope that helps. -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! * Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
[gmx-users] how to calculate kinetic constant?
Hello: I've submit a simulation in gromacs, and I am just wondering how can we calculate kinetic constant for the ligand bound/ubound process? thanks a lot Albert -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! * Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
Re: [gmx-users] how to calculate kinetic constant?
On 2013-10-04 12:30, Albert wrote: Hello: I've submit a simulation in gromacs, and I am just wondering how can we calculate kinetic constant for the ligand bound/ubound process? thanks a lot Albert Check out our recent paper and references therein: http://pubs.acs.org/doi/abs/10.1021/ct400404q -- David van der Spoel, Ph.D., Professor of Biology Dept. of Cell Molec. Biol., Uppsala University. Box 596, 75124 Uppsala, Sweden. Phone: +46184714205. sp...@xray.bmc.uu.sehttp://folding.bmc.uu.se -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! * Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
