You could look at more recent examples in this paper :
https://chemrxiv.org/articles/Blinded_Prediction_of_Protein-Ligand_Binding_Affinity_Using_Amber_Thermodynamic_Integration_for_the_2018_D3R_Grand_Challenge_4/8312375
All of the data files (inputs etc) are available here
https://github.com/csimmerling/D3R-GC4
On Tue, Aug 6, 2019, 7:37 PM Christian Schafmeister <
drschafmeister.gmail.com> wrote:
> Hi folks,
>
> I'm setting up TI calculations with Cando using AMBER.
>
> I'm having a problem where about 1/3rd of the TI calculations are failing
> with the error message below:
>
> ERROR: Calculation halted. Periodic box dimensions have changed too much
> from their initial values.
> (more below)
>
> Could someone point me at a good protocol for carrying out TI calculations
> that avoids this? Or confirm that it's ok to add a constant pressure CPU
> pmemd run between the heating and TI steps.
>
> I am following the protocol described in the AMBER/FEP tutorial (
> http://ambermd.org/tutorials/advanced/tutorial9/#overview)
>
> The steps that I'm using and copied from the benzene/phenol in lysozyme
> example are:
> (1) Create the complex and ligand topology/crd files.
> (2) Minimize the energy of each system.
> (3) Heat each system to 300K
> (4) Pressurize each system to 1atm.
> (5a) For the vdw calculation, for each lambda window, heat each system to
> 300K.
> (6a) (Here it blows up) For the vdw calculation, for each lambda window,
> run a TI calculation.
> (5b) For decharge/recharge stages strip the ligands from the system and
> construct new systems that decharge and recharge the appropriate ligands.
> (6b) For the decharge/recharge stages, for each lambda window heat each
> system
> (7b) (Here it blows up). For the decharge/recharge stages, for each lambda
> window, run a TI calculation.
>
>
> The problem is that a lot of the TI calculations are failing with the error
> message below:
>
> ERROR: Calculation halted. Periodic box dimensions have changed too much
> from their initial values.
> Your system density has likely changed by a large amount, probably from
> starting the simulation from a structure a long way from equilibrium.
>
> [Although this error can also occur if the simulation has blown up for
> some reason]
>
> The GPU code does not automatically reorganize grid cells and thus you
> will need to restart the calculation from the previous restart file.
> This will generate new grid cells and allow the calculation to continue.
> It may be necessary to repeat this restarting multiple times if your
> system
> is a long way from an equilibrated density.
>
> Alternatively you can run with the CPU code until the density has
> converged
> and then switch back to the GPU code.
>
> They are blowing up in the TI step and I'm not sure why, the minimization,
> heating, pressurization, and then heating steps for the TI windows appear
> fine.
> I'm looking for ideas on how to debug the calculation.
> Here is an example of what I'm working with:
> [image: image.png]
> [image: image.png]
>
> This is one of the FEP calculations - the wire-frame is the common parts of
> the molecule and the ball-and-stick are the differences (scmask1 and
> scmask2 respectively). The receptor is 3L9H - a kinesin.
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Received on Tue Aug 06 2019 - 20:00:02 PDT
