From: Jeff Comer (jeffcomer_at_gmail.com)
Date: Wed Aug 18 2021 - 16:24:05 CDT
How long is your simulation?
Even when ABF is converged, the exploration of the collective variable is
limited by free diffusion. Diffusion of helices in a membrane is very slow
(lipid exchange happens on a 10–100 ns timescale). You’d likely have to run
this for several microseconds to get a decent PMF.
You might try find that meta-eABF (
https://urldefense.com/v3/__https://doi.org/10.1021/acs.jpclett.8b01994__;!!DZ3fjg!p--rg2JmHjjsQn3zUlSqmiEYslML__94okujSZ56ZYWn9C22bL21i_Gg37X7O1R5ag$ ) or umbrella sampling will get
you an answer faster, but it’s still going to take a long time to get a
reliable answer because you need to sample many different lipid
arrangements and, again, lipid exchange happens on the 10–100 ns timescale.
Jeff
On Tue, Aug 17, 2021 at 15:44 Ishaan Roy <royi_at_uchicago.edu> wrote:
> Hello,
>
>
>
> I am using eABF on two membrane helices to find the binding energy. During
> the separation runs, the upper boundary for the distance colvar is set to
> 40, the distance value only reaches around 20, even when I increase the
> simulation time. This current maximum it reaches is an inadequate
> separation, since parts of the proteins are still interacting at this point
> and the pmf has not levelled off. When looking at the VMD window, there
> doesn’t seem to be anything obvious that would prevent the ABF from
> separating them further. Any ideas on what might be going on?
>
>
>
> Thanks,
>
> Ishaan
>
>
>
> Here are my colvar settings:
>
>
>
> #############################################################
>
> ## Collective Variables ##
>
> #############################################################
>
>
>
> # Global parameters
>
> ColvarsTrajfrequency 20
>
> Colvarsrestartfrequency 100
>
> analysis on
>
>
>
> colvar {
>
> name dist
>
>
>
> width 0.05
>
>
>
> extendedLagrangian on
>
> extendedFluctuation 0.02
>
>
>
> outputTotalForce on
>
>
>
> lowerboundary 10.0
>
> upperboundary 40.0
>
>
>
> distance {
>
> forceNoPBC yes
>
> group1 {
>
> psfSegID PROA
>
> atomNameResidueRange { CA 32-52 }
>
> }
>
> group2 {
>
> psfSegID PROB
>
> atomNameResidueRange { CA 87-106 }
>
> }
>
> }
>
> }
>
>
>
> colvar {
>
> name sa1
>
> outputValue off
>
>
>
> width 1.0
>
>
>
>
>
> lowerboundary -180.0
>
> upperboundary 180.0
>
>
>
> spinAngle {
>
> atoms {
>
> psfSegID PROA
>
> atomNameResidueRange { CA 32-52}
>
> }
>
> refPositionsFile ../c55_kmeans7_darkblue_F3422_solvated_ionized.pdb
>
> }
>
> }
>
>
>
> colvar {
>
> name sa2
>
> outputValue off
>
>
>
> width 1.0
>
>
>
> lowerboundary -180.0
>
> upperboundary 180.0
>
>
>
> spinAngle {
>
> atoms {
>
> psfSegID PROB
>
> atomNameResidueRange { CA 87-106}
>
> }
>
> refPositionsFile ../c55_kmeans7_darkblue_F3422_solvated_ionized.pdb
>
> }
>
> }
>
>
>
> colvar {
>
> name t1
>
> outputValue off
>
>
>
> width 1.0
>
>
>
>
>
> lowerboundary -1.0
>
> upperboundary 1.0
>
>
>
> tilt {
>
> atoms {
>
> psfSegID PROA
>
> atomNameResidueRange { CA 32-52}
>
> }
>
> refPositionsFile ../c55_kmeans7_darkblue_F3422_solvated_ionized.pdb
>
> }
>
> }
>
>
>
> colvar {
>
> name t2
>
> outputValue off
>
>
>
> width 1.0
>
>
>
> lowerboundary -1.0
>
> upperboundary 1.0
>
>
>
> tilt {
>
> atoms {
>
> psfSegID PROB
>
> atomNameResidueRange { CA 87-106}
>
> }
>
> refPositionsFile ../c55_kmeans7_darkblue_F3422_solvated_ionized.pdb
>
> }
>
> }
>
>
>
> colvar {
>
> name RMSD
>
> width 1.0
>
> outputValue off
>
>
>
> lowerboundary 0.0
>
> upperboundary 5.0
>
>
>
> rmsd {
>
> atoms {
>
> psfSegID PROA PROB
>
> atomNameResidueRange { CA 32-52 }
>
> atomNameResidueRange { CA 87-106}
>
> }
>
> refpositionsfile ../c55_kmeans7_darkblue_F3422_solvated_ionized.pdb
>
> }
>
> }
>
>
>
> #############################################################
>
> ## RESTRAINTS AND PMF
>
> ##############################################################
>
>
>
>
>
> abf {
>
> colvars dist
>
> FullSamples 5000
>
> }
>
>
>
> harmonic {
>
> colvars sa1
>
> forceConstant 0.1
>
> centers 0.0
>
> }
>
>
>
> harmonic {
>
> colvars sa2
>
> forceConstant 0.1
>
> centers 0.0
>
> }
>
>
>
> harmonic {
>
> colvars t1
>
> forceConstant 0.1
>
> centers 1.0
>
> }
>
>
>
> harmonic {
>
> colvars t2
>
> forceConstant 0.1
>
> centers 1.0
>
> }
>
>
>
> harmonic {
>
> colvars RMSD
>
> forceConstant 10.0
>
> centers 0.0
>
> }
>
>
>
>
>
> #############################################################
>
> ### Restraint on Monomer A
>
> ###############################################################
>
>
>
>
>
> colvar {
>
> name Omega
>
> outputValue off
>
> orientation {
>
> atoms {
>
> psfSegID PROB
>
> atomNameResidueRange { CA 87-106 }
>
> }
>
> refpositionsfile ../c55_kmeans7_darkblue_F3422_solvated_ionized.pdb
>
> }
>
> }
>
>
>
> colvar {
>
> name Pin
>
> outputValue off
>
>
>
> width 1.0
>
> lowerboundary 22.9
>
> upperboundary 24.9
>
>
>
> distance {
>
> group1 {
>
> dummyatom (0, 0, 0)
>
> }
>
> group2 {
>
> psfSegID PROB
>
> atomNameResidueRange { CA 87-106 }
>
> }
>
> }
>
> }
>
>
>
> harmonic {
>
> colvars Omega
>
> forceConstant 100.0
>
> centers ( 1.0, 0.0, 0.0, 0.0 )
>
> }
>
>
>
>
>
> harmonic {
>
> colvars Pin
>
> forceConstant 100.0
>
> centers 23.9
>
> }
>
-- –––––––––––––––––––––––––––––––––––——————— Jeffrey Comer, PhD Associate Professor Department of Anatomy and Physiology Kansas State University Office: P-213 Mosier Hall Phone: 785-532-6311 Website: https://urldefense.com/v3/__http://jeffcomer.us__;!!DZ3fjg!p--rg2JmHjjsQn3zUlSqmiEYslML__94okujSZ56ZYWn9C22bL21i_Gg37W7Pflqww$
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