Re: [gmx-users] PMF calculation by umbrella sampling simulations
On 4/30/15 4:12 PM, MPI wrote: Hi Justin, Thanks for your explanation. (1) In the tutorial, then what is a good approximate value of free energy ? if one follows the protocol. Is -37 or so kcal mol^-1 ? That is what you should get from the tutorial. Here, 26 windows of COM distances are used, each for 10 ns simulation. (2) In your original paper, -50.5 kcal mol^-1 is the free energy for dissociation of a single peptide from protofibril. In this full preparation, you used 31-window setup, each for 10 ns simulation. I've been aware of the difference between 26 and 31 windows but questions are First, if one obtains a reasonable histogram like https://docs.google.com/file/d/0B9uTAq1wCc1fVkRPY2FrTExFcmM/edit ,how can one tell whether if the system needs more windows ? because these overlap windows look appropriate. Simply looking at histograms only tells you if you're in the ballpark. g_wham has a very nice set of options for doing error analysis. You'll note there is minimal overlap in a few of your windows; these would correspond to regions of the reaction coordinate with large error. If you do the bootstrap analysis you will see this. Second, after full preparation, how did you know the free energy of -50.5 or so is a GOOD value ? I did error analysis :) See details in the paper. Third, comparing a coarse ( the tutorial) with a full preparation ( your original paper), it is somehow unclear that the number of windows can cause a significant difference of 13 kcal mol^-1 since it runs independently for 10 ns in each window. Please see PMF curve attached in a simulation of 26 windows, each for 10 ns. https://drive.google.com/open?id=0B9uTAq1wCc1fSUtwSVh4cnFpZVEauthuser=0 The PMF curve looks reasonable except when it converges to 37.5 kcal mol^-1 or so. There is no clear energy minimum there and you haven't done error analysis, so looks good doesn't really mean anything. -Justin -- == Justin A. Lemkul, Ph.D. Ruth L. Kirschstein NRSA Postdoctoral Fellow Department of Pharmaceutical Sciences School of Pharmacy Health Sciences Facility II, Room 629 University of Maryland, Baltimore 20 Penn St. Baltimore, MD 21201 jalem...@outerbanks.umaryland.edu | (410) 706-7441 http://mackerell.umaryland.edu/~jalemkul == -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org.
Re: [gmx-users] PMF calculation by umbrella sampling simulations
Hi Justin, Thanks for your explanation. (1) In the tutorial, then what is a good approximate value of free energy ? if one follows the protocol. Is -37 or so kcal mol^-1 ? Here, 26 windows of COM distances are used, each for 10 ns simulation. (2) In your original paper, -50.5 kcal mol^-1 is the free energy for dissociation of a single peptide from protofibril. In this full preparation, you used 31-window setup, each for 10 ns simulation. I've been aware of the difference between 26 and 31 windows but questions are First, if one obtains a reasonable histogram like https://docs.google.com/file/d/0B9uTAq1wCc1fVkRPY2FrTExFcmM/edit ,how can one tell whether if the system needs more windows ? because these overlap windows look appropriate. Second, after full preparation, how did you know the free energy of -50.5 or so is a GOOD value ? Third, comparing a coarse ( the tutorial) with a full preparation ( your original paper), it is somehow unclear that the number of windows can cause a significant difference of 13 kcal mol^-1 since it runs independently for 10 ns in each window. Please see PMF curve attached in a simulation of 26 windows, each for 10 ns. https://drive.google.com/open?id=0B9uTAq1wCc1fSUtwSVh4cnFpZVEauthuser=0 The PMF curve looks reasonable except when it converges to 37.5 kcal mol^-1 or so. Thanks, Dewey Justin Lemkul wrote: On 4/30/15 12:43 AM, MPI wrote: Dear Users, With GMX 4.6.5, I tried to reproduce a system of the dissociation of a single peptide in an AB42 protofibril with PMF (potential of mean force) calculation in Justin's umbrella sampling tutorial. He derived the binding energy from PMF from a series of umbrella sampling simulations and obtained a value of free energy close to -50.5 kcal mol-1. But I got a value of -37.5 kcal mol-1 after PMF curve was converged. The value difference is significant and this raises two questions. What dose cause this difference of ~13 kcal mol -1 ? although I used GPU for calculations, which is the only modification (cutoff-scheme = Verlet). What is a reasonable range of binding free energy in this case of AB42 protofibril ? As I state in the tutorial and as I have said multiple times on the list (even just a few days ago!), you will not produce the PMF profile shown in the tutorial unless you follow the exact protocol in the paper (which is linked in the tutorial). The value of -37 or so is what you will achieve if you do what the tutorial says, which is a quick and dirty approximation of the protocol. The full preparation (100 ns of MD on the protofibril, followed by a special window setup described in the paper to adequately sample small COM distances) will yield the quoted value. -Justin -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org.
[gmx-users] PMF calculation by umbrella sampling simulations
Dear Users, With GMX 4.6.5, I tried to reproduce a system of the dissociation of a single peptide in an AB42 protofibril with PMF (potential of mean force) calculation in Justin's umbrella sampling tutorial. He derived the binding energy from PMF from a series of umbrella sampling simulations and obtained a value of free energy close to -50.5 kcal mol-1. But I got a value of -37.5 kcal mol-1 after PMF curve was converged. The value difference is significant and this raises two questions. What dose cause this difference of ~13 kcal mol -1 ? although I used GPU for calculations, which is the only modification (cutoff-scheme = Verlet). What is a reasonable range of binding free energy in this case of AB42 protofibril ? The umbrella histogram showing the overlap between window looks reasonable. See attached here. https://drive.google.com/open?id=0B9uTAq1wCc1fVkRPY2FrTExFcmMauthuser=0 Suggestions or opinions are appreciated. Thanks, Dewey -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org.
