Re: [AMBER] Combining CpHMD and aMD

From: Cruzeiro,Vinicius Wilian D <vwcruzeiro.ufl.edu>
Date: Mon, 28 Jan 2019 14:22:58 +0000

Hello Cecilia,


The explicit solvent CpHMD implementation is actually hybrid. This is because during the protonation state change attempts the waters are stripped and the monte carlo probabilities are computed in implicit solvent. For this reason, the pKa predictions in explicit solvent generally follow the same trends of the implicit solvent simulations. I would say that the biggest advantage of doing explicit solvent CpHMD is on the ensamble of coordinates generated, that does take into consideration explicit waters. The use of implicit solvent imposes some limitations/inaccuracies even in regular MD simulations.


I hope this helps,

All the best,


VinÝcius Wilian D. Cruzeiro

PhD Candidate
Department of Chemistry, Physical Chemistry Division
University of Florida, United States

Voice: +1(352)846-1633

________________________________
From: Cecilia Lindgren <cecilia.lindgren.umu.se>
Sent: Monday, January 28, 2019 8:13:49 AM
To: AMBER Mailing List
Subject: Re: [AMBER] Combining CpHMD and aMD

Hello VinÝcius,



Ok, then I will run the simulations with implicit water instead. Do you know what effect that will have, that is, will the results from implicit water simulations be comparable to explicit water MD simulations? I have not seen much about that.



Thank you for your reply!



Best regards,

Cecilia



_________________________________________________

Cecilia Lindgren, Ph.D.

Umeň University

Department of Chemistry

Linnaeus vńg

SE-901 87 Umeň

Sweden

cecilia.lindgren.umu.se







-----Original Message-----

From: Cruzeiro,Vinicius Wilian D <vwcruzeiro.ufl.edu>

Sent: den 28 januari 2019 13:36

To: AMBER Mailing List <amber.ambermd.org>

Subject: Re: [AMBER] Combining CpHMD and aMD



Hello Cecilia,



I (highly) suspect that your issue is coming from the solvent relaxation stage. In the constant pH code, once a protonation state change is accepted some MD steps are executed where the solute degrees of freedom are frozen. This stage could me messing with the aMD actions. If my hypothesis is correct, running without solvent relaxation (ntrelax=0) should be fine and it would explain why CpHMD+aMD works in Implicit solvent (as you mentioned in your first email). As you shouldnĺt run CpHMD without solvent relaxation, some coding adjustments are necessary.



All the best,





VinÝcius Wilian D Cruzeiro



PhD Candidate

Department of Chemistry, Physical Chemistry Division University of Florida, United States



Voice: +1(352)846-1633<tel:+1(352)846-1633>



On Jan 28, 2019, at 2:27 AM, Cecilia Lindgren <cecilia.lindgren.umu.se<mailto:cecilia.lindgren.umu.se>> wrote:



Hello VinÝcius,



Thank you for your reply. I have tried to run it with only aMD as well, and then it looks ok. So it is only when I combine the two that I experience this odd behavior.



Best regards,

Cecilia



_________________________________________________

Cecilia Lindgren, Ph.D.

Umeň University

Department of Chemistry

Linnaeus vńg

SE-901 87 Umeň

Sweden

cecilia.lindgren.umu.se<mailto:cecilia.lindgren.umu.se>





-----Original Message-----

From: Cruzeiro,Vinicius Wilian D <vwcruzeiro.ufl.edu<mailto:vwcruzeiro.ufl.edu>>

Sent: den 25 januari 2019 23:00

To: 'amber.ambermd.org<mailto:amber.ambermd.org>' <amber.ambermd.org<mailto:amber.ambermd.org>>

Subject: Re: [AMBER] Combining CpHMD and aMD



Hello Cecilia,





Combining different techniques in Amber is something not necessarily trivial. I am aware of some cases in which additional coding would be required for the combination of techniques to work properly. However, I have never attempted performing CpHMD with aMD, thus I do not know before hand of any eventual issues that would only raise when both are executed together.





With that in mind, I would suggest you to run your simulation that fail again but with no CpHMD (icnstph=0). This would tell you to if your issue happens with aMD or only when CpHMD and aMD are executed together.





I hope this helps,



All the best,





VinÝcius Wilian D. Cruzeiro



PhD Candidate

Department of Chemistry, Physical Chemistry Division University of Florida, United States



Voice: +1(352)846-1633



________________________________

From: Cecilia Lindgren <cecilia.lindgren.umu.se<mailto:cecilia.lindgren.umu.se>>

Sent: Thursday, January 24, 2019 10:37:26 AM

To: 'amber.ambermd.org<mailto:amber.ambermd.org>'

Subject: [AMBER] Combining CpHMD and aMD



Dear Amber Users,



I am trying to run constant pH MD (CpHMD) with AMBER, in combination with accelerated MD (aMD). I am using explicit water.

However, when I use these settings the protein unfolds, as if it is being "pulled apart". I have attached a figure from the beginning of the MD simulation and from when the protein starts to unfold. This simulation included 10 ns of CpHMD, followed by 10 ns of CpHMD in combination with aMD. The unfolding starts almost immediately after aMD is started.

I have restarted the simulation twice but the problem remains.



If I use CpHMD without trying to combine it with aMD, it looks ok during the 70 ns I have run it for. (However, it is clearly more dynamic than when running normal MD.)



Has anyone else tried this? I can only find examples of implicit MD where CpHMD and aMD are combined. Is it possible, or do I need to use implicit water instead of explicit in case I want to combine CpHMD with aMD?



I have also attached the settings I use for the production run.



Best regards,

Cecilia



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