Umbrella Sampling Methodology

From: Charlie Forde (charlie.forde_at_hotmail.com)
Date: Mon Aug 16 2010 - 06:23:15 CDT

Dear NAMD community,

I have no experience in applying umbrella sampling but nonetheless I wish to carry out such a calculation using NAMD. I basically wish to calculate the PMF as a molecule is displaced along the z direction (the reaction coordinate) from a surface.

As I understand it, what I need to do is to preform a series of equilibrium calculations with the molecule placed at increasing discrete distances (windows) from the surface. In addition the center of mass of the molecule has to be restrained (achieved using colvars, see below) close to its starting position (using forceConstant with its magnitude determined through trial and error) in each window. Having completed the simulations I should output the time series of the z component of the center of mass of the molecule (which can be done using the script in the VMD manual) for each window.

I should then generate a series of histograms to ensure that there is sufficient overlap between the windows (using for example Ting Wangs script, see http://projects.eml.org/mcm/people/wang/PMF/tutorial.html ), having satisfied this requirement I can then proceed to generate the PMF by using a WHAM program such as Alan Grossfield's (http://membrane.urmc.rochester.edu/Software/WHAM/WHAM.html).

My questions are:
1) Is the methodology that I have outlined above correct?
2) I will apply the harmonic restraints via the colvar options, is this the correct method and is my colvar script correct?
3) Are there any guideline on the optimum length of simulations. I am concerned that if the simulations are too long then there will be little phase space overlap between windows while if the simulations are too short then the molecule would not be equilibrated.
4) Are there guidelines as to the number of windows per nm displaced or is this to be determined afterwards for viewing the generated histograms?

Finally I would like to note that the NAMD/VMD tutorials currently available are exceptionally well written and enable those of us with more modest capabilities to preform worthwhile studies, while I believe that an umbrella sampling tutorial would be a welcomed addition. I realize that my system could also be addressed (more robustly and intuitively) using steered molecular dynamics and the Jarzynski equality but he who pays the salary is partial to umbrella sampling.

Regards,

Charlie

------ colvar additions to my.conf file ------

colvars on

colvarsConfig my_colvars

----------------------------------------------------

++++++++++ my_colvars +++++++++++

colvar {

      name myCOM

         distance {

                   group1 { atomNumbersRange 24 - 1231}

                   group2 { dummyAtom ( 30.31, 28.80, 15.35 )}

# A dummyAtom containing the center of mass of my molecule.

                 }

       }

harmonic {

          colvars myCOM

          centers 0

          forceConstant 42.0

         }

++++++++++++++++++++++++++++++++++++++++++++++++
                                               

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