Date: Mon, 11 Jan 2021 17:41:36 +0000
Hello,
Have you gone through this very recent article?
https://pubs.acs.org/doi/pdf/10.1021/acs.jcim.0c00613
This one helped to clear out a lot of doubts/haziness I had regarding setting up a successful TI experiment.
It may be helpful.
I will go through the input files, and let you know if I see anything out of the ordinary.
Best wishes,
Debarati
From: Delwakkada Liyanage, Senal Dinuka<mailto:sdd313.msstate.edu>
Sent: 11 January 2021 11:16
To: Debarati DasGupta<mailto:debarati_dasgupta.hotmail.com>; David A Case<mailto:david.case.rutgers.edu>
Cc: AMBER Mailing List<mailto:amber.ambermd.org>
Subject: Re: [AMBER] TI simulation blowing up with pmemd.CUDA
Hello Dr. DasGupta and Dr. Case,
Thank you very much, Dr. Case, for your invaluable ideas.
I'm trying to calculate ABFE for a DNA/ligand system. I have used a two-step transformation because my system is a G-quadruplex/ligand system where the ligand carries a positive(+) 4 charge. I feel that a concerted protocol might be unreliable under these conditions owing to numerical instabilities. So far, I have only modeled the later part (8742 atoms) of the thermodynamic cycle (the ligand decoupling from the solvent) to be sure of the protocol before moving to decoupling from the solvated complex. Thus, the following inputs are made in such a way. The starting coordinates for decharging step have been obtained after a brief equilibration period without using any TI parameters. I have modified the scripts given under Amber-TI tutorials for my convenience. I have amended the respective scripts and simulation inputs for a fresh start. Furthermore, I have amended my final restart for the decharging endpoint which was used as the starting point for LJ decoupling. I really appreciate your insight into tackling TI.
Thank you
Senal
From: Debarati DasGupta <debarati_dasgupta.hotmail.com>
Sent: Monday, January 11, 2021 7:52 AM
To: AMBER Mailing List <amber.ambermd.org>
Subject: Re: [AMBER] TI simulation blowing up with pmemd.CUDA
Hello Senal,
I hope you are doing good.
Welcome to the “tricky-TI” project.
Well, I have been doing some TI calculations in AMBER20 since last 1 year, and I have faced many issues and a lot of help/directions were given by Prof Case
( I genuinely thank him for that).
What are your system details? Total number of atoms? Are you doing RBFE or ABFE? What’s the process for which you are trying to calculate the FE?
I have always done the concerted protocol, where you decharge and remove the LJ interactions in 1 step.. Yes it can be error prone but using the smoothstep softcore (SSC P=2) potentials ( search Darrin York latest TI papers published in June/July 2020 JCIM) , a lot of those issues got resolved. I would also recommend doing a non-TI, simple conventional MD equilibration and production to help alleviate unfavourable interactions, high energies, steric clashes, prior to setting up the TI calculations. I can provide you some more tips I used, depending on what system and what FE you are trying to calculate. If possible switch to AMBER20, just switching from AMBER18 to20 solved some of my TI based problems.
Best wishes
Debarati
Sent: 10 January 2021 15:08
To: AMBER Mailing List<mailto:amber.ambermd.org>
Subject: Re: [AMBER] TI simulation blowing up with pmemd.CUDA
Hello Dr. Case,
The unit cell dimensions are as 52.981 x 42.118 x 52.650 angstroms and the amber 18 version have been updated to the latest. There wasn't any issue during the decharging step throughout the lambda values. So, I'm unsure as to why a sudden energy burst should happen at the second lambda point simulation for vdW removal.
Following is the terminal output I obtained from running my script on the CPU code.
simulating vdw_bonded
changing directory to lambda = 0.00922
equilibration for 350 ps
equilibration for 1 ns
sampling for 10 ns
changing directory to lambda = 0.04794
equilibration for 350 ps
equilibration for 1 ns
sampling for 10 ns
Error: an illegal memory access was encountered launching kernel kNLSkinTest
Thank you
Senal Liyanage
________________________________
From: David A Case <david.case.rutgers.edu>
Sent: Sunday, January 10, 2021 1:28 PM
To: AMBER Mailing List <amber.ambermd.org>
Subject: Re: [AMBER] TI simulation blowing up with pmemd.CUDA
On Sun, Jan 10, 2021, Delwakkada Liyanage, Senal Dinuka wrote:
>
>I am trying to do TI in Amber18 with pmemd.cuda. The system is a small
>porphyrin ligand ( C44H38N8), prepared in a 16 A TIP3P water box.
What are the unit cell dimensions for your system? Small systems can be
unstable with with our GPU code, but I'm not sure when the relevant error
message was inserted into the code.
For sure, be certain that you have applied all updates to the code. If it's
not something obvious, you will probably need to upgrade to Amber20: there
have been significant changes in how softcore TI is done, and not all of the
fixes have been back-ported to Amber18.
....dac
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