From: Grace Brannigan (grace.brannigan_at_rutgers.edu)
Date: Tue Jun 21 2016 - 13:03:24 CDT
Hi Brian,
As a decade-long user of the alchemy code, I certainly welcome improvements
to consistency and accuracy, and appreciate you working to implement fixes.
It is alarming, though, to hear that changes are being committed casually
and without documentation. A few months ago, for instance, my postdoc Reza
Salari observed discrepancies of ~30,000 kcal/mol in FEP output from the
development version. That was hard to miss, but naturally makes us wonder
about less obvious bugs.
Even undocumented fixes can introduce unexpected discrepancies compared to
previous results, which can take a user some time to track down if they
don't know where to look. You might know it's an improvement - but the
user doesn't.
So, I'd like to request that you be considerate to the numerous research
groups using the FEP features when choosing to commit changes. And let me
know if you need some unusual test cases...
Thanks,
-- Grace Brannigan, Ph.D. Assistant Professor Center for Computational and Integrative Biology (CCIB) & Department of Physics Rutgers University, Camden, NJ (856)225-6780 http://branniganlab.wordpress.com On Tue, Jun 21, 2016 at 10:48 AM, Jérôme Hénin <jerome.henin_at_ibpc.fr> wrote: > Brian, thanks for outlining those issues, in particular missing docs. I > can't recommend enough that the docs be updated at the same time as the > features themselves. It's vital for users of development versions, and it's > the best time to do it as a developer as well - not least, it removes the > risk that some things never get documented at all, like the WCA features. > > Interactions with the pressure control, both through the kinetic pressure > term for vanishing atoms (an issue you mentioned earlier) or long-range > corrections, are among the subtleties that make it so complicated to > maintain a solid alchemy code. Phrases like "should work more or less ok > now" are pretty worrying for a user to read. They are also a reminder that > we lack test cases for this code. > > I know that you need to get some science done, but I hope you can find > some time to clean up the existing code, and build tests to ensure its > robustness. > > Jerome > > > On 21 June 2016 at 14:36, Brian Radak <brian.radak.accts_at_gmail.com> wrote: > >> >> >> On 06/20/2016 05:09 PM, Yue Qian wrote: >> >>> Dear NAMD users, >>> >>> I am currently using NAMD to carry out free energy of binding >>> calculations of a protein-ligand system. I have encountered several >>> problems regrading the long-range LJ corrections. I have googled for >>> certain issues but couldn't find relevant, informative discussions. >>> >>> This is what I found on the manual: >>> LJcorrection: Description: Apply an analytical correction to the >>> reported vdW energy and virial that is equal to the amount lost due to >>> switching and cutoff of the LJ potential. The correction will use the >>> average of vdW parameters for all particles in the system and assume a >>> constant, homogeneous distribution of particles beyond the switching >>> distance. See [60] for details (the equations used in the NAMD >>> implementation are slightly different due to the use of a different >>> switching function). Periodic boundary conditions are required to make use >>> of tail corrections. LJcorrection as implemented is inconsistent with >>> vdwForceSwitching. >>> >>> Here are my questions: >>> 1. To turn on the long-range LJ correction, is "LJcorrection yes" is >>> the only thing I need to do? (From the manual, I noticed that "LJcorrection >>> as implemented is inconsistent with vdwForceSwitching." vdwForceSwitching >>> was kept off.) I have tested this protocol in unbound state calculation >>> with only the solute molecule and TIP3 water molecules with LJcorrection on >>> and off. However, I did not observe significant difference, which was >>> expected to be around 0.5 ~ 0.6 kcal/mol. But with "Ewald off", the >>> calculation result was ~0.8kcal/mol more positive. This patten applies to >>> different cutoffs, from 8 Ang to 12 Ang. >>> >>> Correct, "LJCorrection yes" or "LJCorrection on" will apply the >> correction. As of 2.11 there actually is now a vdwForceSwitching compatible >> correction, I just haven't updated the documentation yet (sorry!). If a >> warning message still states this incompatibility, then it is not present, >> because I also removed that message in the update. >> >> The new code also improves consistency in conjunction with alchemical >> endpoints, but might not work as expected with the (also mostly >> undocumented) WCA FEP code. Standard FEP and TI should work more or less ok >> now. >> >> In general, such a correction will not significantly change free energies >> unless the solute rather very large. Even then I might only expect sub >> kcal/mol changes. >> >> The main changes I expected when I did all of this was to get different >> densities during an NpT equilibration. In general the correction increases >> density by ~5%. >> >> 2. According to the manual, the LJcorrction option assumes a homogeneous, >>> isotropic environment which only applies to unbound state calculation. To >>> be able to apply to bound state calculation, heterogenous, nonisotropic >>> environment needs to be considered. The cited paper (J. Phys. Chem. B, Vol. >>> 111, No. 45, 2007) covered both scenarios. But GROMACS was used in their >>> work. I was wondering if there's anyway to incorporate such methods in NAMD. >>> >> The main options here are to apply a Lennard-Jones Ewald approach (not >> available in NAMD) or else to use the perturbation-like method by >> re-evaluating the energy with a larger cutoff. The latter is doable but has >> never been automated in NAMD to my knowledge (I suppose we could give this >> a try if there is interest). >> >> >>> Any clue is appreciated. Thank you very much. >>> >>> Best, >>> Yue >>> >>> -- >>> Yue Qian >>> >>> >> -- >> Brian Radak >> Postdoctoral Scholar >> Gordon Center for Integrative Science, W323A >> Department of Biochemistry & Molecular Biology >> University of Chicago >> 929 E. 57th St. >> Chicago, IL 60637-1454 >> Tel: 773/834-2812 >> email: radak_at_uchicago.edu >> >> -- >> <radak_at_uchicago.edu> >> <radak_at_uchicago.edu> >> Grace Brannigan, Ph.D. >> Assistant Professor >> Center for Computational and Integrative Biology (CCIB) & >> Department of Physics >> Rutgers University, Camden, NJ >> (856)225-6780 >> <radak_at_uchicago.edu> >> <radak_at_uchicago.edu>http://branniganlab.wordpress.com >> >
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