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From: Carlos Simmerling <carlos.simmerling.gmail.com>

Date: Wed, 3 Feb 2021 12:17:26 -0500

I agree with Dave, if you aren't familiar with NEB doing such a large

system can be very difficult to debug. I think it's best to start with

something simpler like alanine dipeptide (done in our Bergonzo et al NEB

paper https://onlinelibrary.wiley.com/doi/abs/10.1002/qua.22405 ), or model

systems like those studied by Delaram et al (

https://pubs.acs.org/doi/abs/10.1021/acs.jctc.9b00329; her phd

dissertation is very detailed and is available here

https://ufdc.ufl.edu/UFE0055988/00001).

On Wed, Feb 3, 2021 at 12:02 PM 李明玉 <santaclaus.sjtu.edu.cn> wrote:

*> Hi Carlos,
*

*>
*

*> Thank you for your prompt reply.
*

*>
*

*> Your suggestion works.
*

*> Although I have read the methods of the following article carefully, I am
*

*> still not confident with the parameters setting for my large protein
*

*> systems.
*

*>
*

*> I would appreciate it if you could give me the ".in" files for NEB four
*

*> steps in Amber (1heat.in, 2equil, 3anneal.in, 4cool.in).
*

*> Then I could have a deep understanding of NEB.
*

*>
*

*> Free Energy Landscapes for RBD Opening in SARS-CoV-2 Spike Glycoprotein
*

*> Simulations Suggest Key Interactions and a Potentially Druggable
*

*> Allosteric
*

*> Pocket. <https://doi.org/10.26434/chemrxiv.13502646> Lucy Fallon, Kellon
*

*> Belfon, Lauren Raguette, Yuzhang Wang, Christopher Corbo, Darya
*

*> Stepanenko,
*

*> Abbigayle Cuomo, Jose Guerra, Stephanie Budhan, Sarah Varghese, Robert
*

*> Rizzo, Carlos Simmerling, *preprint*
*

*>
*

*>
*

*> Best wishes,
*

*>
*

*> Pineapple
*

*>
*

*> 发件人: "Carlos Simmerling" <carlos.simmerling.gmail.com>
*

*> 收件人: "amber" <amber.ambermd.org>
*

*> 发送时间: 星期三, 2021年 2 月 03日 下午 9:17:30
*

*> 主题: Re: [AMBER] Nudged Elastic Band solvent choice and initial heating
*

*> problem
*

*>
*

*> The first thing you should do is to turn on shake (ntc). is there a reason
*

*> it is off? Explicit water models are usually rigid and require shake.
*

*> then see how things go. You might want to look at other papers with
*

*> explicit solvent NEB, our lab has published several, a few are listed
*

*> below.
*

*>
*

*> Free Energy Landscapes for RBD Opening in SARS-CoV-2 Spike Glycoprotein
*

*> Simulations Suggest Key Interactions and a Potentially Druggable
*

*> Allosteric
*

*> Pocket. <https://doi.org/10.26434/chemrxiv.13502646> Lucy Fallon, Kellon
*

*> Belfon, Lauren Raguette, Yuzhang Wang, Christopher Corbo, Darya
*

*> Stepanenko,
*

*> Abbigayle Cuomo, Jose Guerra, Stephanie Budhan, Sarah Varghese, Robert
*

*> Rizzo, Carlos Simmerling, *preprint*
*

*>
*

*>
*

*> *DNA Deformation-Coupled Recognition of 8‑Oxoguanine: Conformational
*

*> Kinetic Gating in Human DNA Glycosylase
*

*> <https://doi.org/10.1021/jacs.6b11433>. Li, H., Endutkin, A., Bergonzo,
*

*> C.,
*

*> Fu, L., Grollman, A., Zharkov, D., Simmerling, C., Journal of the American
*

*> Chemical Society, 2017, 139 (7), 2682-2692*
*

*>
*

*>
*

*> *Rational modulation of the induced-fit conformational change for
*

*> slow-onset inhibition in M. tuberculosis InhA
*

*> <https://doi.org/10.1021/acs.biochem.5b00284>. Lai, C-T., Li, H; Yu, W.,
*

*> Shah, S., Bommineni, G., Perrone, V., Garcia-Diaz, M., Tonge, P.,
*

*> Simmerling, C., Biochemistry, 2015, 54 (30), 4683-4691*
*

*>
*

*>
*

*>
*

*> On Wed, Feb 3, 2021 at 7:13 AM 李明玉 <santaclaus.sjtu.edu.cn> wrote:
*

*>
*

*> > Hi Amber users,
*

*> >
*

*> > I am trying to perform nudged elastic band method (NEB) on a large
*

*> > 1618-residue protein.
*

*> >
*

*> > I am using the same NEB parameters and protocol as the Amber tutorial
*

*> A5,
*

*> > except for those relating to implicit solvent. Here, I applied the
*

*> explicit
*

*> > solvent. All the initial structures have been carefully prepared and
*

*> > minimized.
*

*> > However, when I checked the output of the initial heating MD, the
*

*> > individual replicate energies were **** (change the cut to 9999 also
*

*> cause
*

*> > this problem).
*

*> > Please see the output 1 below.
*

*> >
*

*> > Then I tried NEB with implicit solvent , adopting the same parameter as
*

*> > the tutorial, the energy problem seems to be solved.
*

*> > I found the energy of this system was small without plenty of
*

*> > solvent-solvent interactions. That may be the reason to solve the
*

*> problem.
*

*> > Please see the output 2 below.
*

*> >
*

*> >
*

*> > Therefore, I have the following questions:
*

*> > For large protein systems, what is the best type of solvent to choose?
*

*> > In my opinion, although there are lots of solvent-solvent interactions,
*

*> > the explicit solvent would still be better since it is close to the
*

*> > reality.
*

*> > If so, how to solve the initial heating problems with the explicit
*

*> > solvent?
*

*> > My opinion might be ill-considered for I'm new to MD.
*

*> >
*

*> >
*

*> > Any suggestions on what I might have done wrong would be much
*

*> appreciated.
*

*> >
*

*> > Many thanks,
*

*> >
*

*> > Pineapple
*

*> >
*

*> >
*

*> > Output1:
*

*> >
*

*> > -------------------------------------------------------
*

*> > Amber 18 PMEMD 2018
*

*> > -------------------------------------------------------
*

*> >
*

*> > Here is the input file:
*

*> > &cntrl
*

*> > imin = 0, irest = 0,
*

*> > ntc=1, ntf=1,
*

*> > ntpr=1000, ntwx=10000,
*

*> > ntb = 1, igb=0, cut=10, rgbmax=10,
*

*> > nstlim = 1000000, nscm=0,
*

*> > dt = 0.0005, ig=-1,
*

*> > ntt = 3, gamma_ln=1000.0,
*

*> > tempi=0.0, temp0=300.0,
*

*> > tgtfitmask=":1-1618.CA",
*

*> > tgtrmsmask=":1-1618",
*

*> > ineb = 1,skmin = 10,skmax = 10,
*

*> > nmropt=1,
*

*> > /
*

*> > &wt type='TEMP0', istep1=0,istep2=800000,
*

*> > value1=0.0, value2=300.0
*

*> > /
*

*> > &wt type='END'
*

*> > /
*

*> >
*

*> > |------------------- GPU DEVICE INFO --------------------
*

*> > |
*

*> > | Task ID: 0
*

*> > | CUDA_VISIBLE_DEVICES: 0,1,2,3,4,5,6,7
*

*> > | CUDA Capable Devices Detected: 8
*

*> > | CUDA Device ID in use: 0
*

*> > | CUDA Device Name: Tesla V100-SXM2-16GB
*

*> > | CUDA Device Global Mem Size: 16130 MB
*

*> > | CUDA Device Num Multiprocessors: 80
*

*> > | CUDA Device Core Freq: 1.53 GHz
*

*> > |
*

*> > |--------------------------------------------------------
*

*> > |---------------- GPU PEER TO PEER INFO -----------------
*

*> > |
*

*> > | Peer to Peer support: ENABLED
*

*> > |
*

*> > |--------------------------------------------------------
*

*> >
*

*> >
*

*> --------------------------------------------------------------------------------
*

*>
*

*> >
*

*> > 4. RESULTS
*

*> >
*

*> --------------------------------------------------------------------------------
*

*>
*

*> >
*

*> >
*

*> > The following selection will be used for NEB structure fitting
*

*> > Mask ":1-1618.CA" matches 1618 atoms
*

*> > The following selection will be used for NEB force application
*

*> > Mask ":1-1618" matches 25494 atoms
*

*> >
*

*> > Last atom in NEB fitmask or rmsmask is 25494
*

*> >
*

*> > NSTEP = 0 TIME(PS) = 0.000 TEMP(K) = 0.00 PRESS = 0.0
*

*> > Etot = -686665.5046 EKtot = 0.0000 EPtot = -686665.5046
*

*> > BOND = 49737.9500 ANGLE = 16906.3886 DIHED = 21361.6559
*

*> > 1-4 NB = 74233.0973 1-4 EEL = 74040.2101 VDWAALS = 69345.1204
*

*> > EELEC = -992289.9269 EHBOND = 0.0000 RESTRAINT = 0.0000
*

*> > NEB replicate breakdown:
*

*> > Energy for replicate 1 = -686665.5046
*

*> > Energy for replicate 2 = -686665.5046
*

*> > Energy for replicate 3 = -686665.5046
*

*> > Energy for replicate 4 = -686665.5046
*

*> > Energy for replicate 5 = -686665.5046
*

*> > Energy for replicate 6 = -686665.5046
*

*> > Energy for replicate 7 = -686665.5046
*

*> > Energy for replicate 8 = -686665.5046
*

*> > Energy for replicate 9 = -686665.5046
*

*> > Energy for replicate 10 = -686665.5046
*

*> > Energy for replicate 11 = -686665.5046
*

*> > Energy for replicate 12 = -686665.5046
*

*> > Energy for replicate 13 = -686665.5046
*

*> > Energy for replicate 14 = -686665.5046
*

*> > Energy for replicate 15 = -686665.5046
*

*> > Energy for replicate 16 = -686665.5046
*

*> > Energy for replicate 17 = -543804.4518
*

*> > Energy for replicate 18 = -543804.4518
*

*> > Energy for replicate 19 = -543804.4518
*

*> > Energy for replicate 20 = -543804.4518
*

*> > Energy for replicate 21 = -543804.4518
*

*> > Energy for replicate 22 = -543804.4518
*

*> > Energy for replicate 23 = -543804.4518
*

*> > Energy for replicate 24 = -543804.4518
*

*> > Energy for replicate 25 = -543804.4518
*

*> > Energy for replicate 26 = -543804.4518
*

*> > Energy for replicate 27 = -543804.4518
*

*> > Energy for replicate 28 = -543804.4518
*

*> > Energy for replicate 29 = -543804.4518
*

*> > Energy for replicate 30 = -543804.4518
*

*> > Energy for replicate 31 = -543804.4518
*

*> > Energy for replicate 32 = -543804.4518
*

*> > Total Energy of replicates = *************
*

*> >
*

*> ------------------------------------------------------------------------------
*

*>
*

*> >
*

*> >
*

*> > NMR restraints: Bond = 0.000 Angle = 0.000 Torsion = 0.000
*

*> >
*

*> ===============================================================================
*

*>
*

*> >
*

*> >
*

*> > NSTEP = 1000 TIME(PS) = 0.500 TEMP(K) = 0.00 PRESS = 0.0
*

*> > Etot = -686665.5046 EKtot = 0.0000 EPtot = -686665.5046
*

*> > BOND = 49737.9500 ANGLE = 16906.3886 DIHED = 21361.6559
*

*> > 1-4 NB = 74233.0973 1-4 EEL = 74040.2101 VDWAALS = 69345.1204
*

*> > EELEC = -992289.9269 EHBOND = 0.0000 RESTRAINT = 0.0000
*

*> > NEB replicate breakdown:
*

*> > Energy for replicate 1 = -686665.5046
*

*> > Energy for replicate 2 = *************
*

*> > Energy for replicate 3 = *************
*

*> > Energy for replicate 4 = *************
*

*> > Energy for replicate 5 = *************
*

*> > Energy for replicate 6 = *************
*

*> > Energy for replicate 7 = *************
*

*> > Energy for replicate 8 = *************
*

*> > Energy for replicate 9 = *************
*

*> > Energy for replicate 10 = *************
*

*> > Energy for replicate 11 = *************
*

*> > Energy for replicate 12 = *************
*

*> > Energy for replicate 13 = *************
*

*> > Energy for replicate 14 = *************
*

*> > Energy for replicate 15 = *************
*

*> > Energy for replicate 16 = *************
*

*> > Energy for replicate 17 = *************
*

*> > Energy for replicate 18 = *************
*

*> > Energy for replicate 19 = *************
*

*> > Energy for replicate 20 = *************
*

*> > Energy for replicate 21 = *************
*

*> > Energy for replicate 22 = *************
*

*> > Energy for replicate 23 = *************
*

*> > Energy for replicate 24 = *************
*

*> > Energy for replicate 25 = *************
*

*> > Energy for replicate 26 = *************
*

*> > Energy for replicate 27 = *************
*

*> > Energy for replicate 28 = *************
*

*> > Energy for replicate 29 = *************
*

*> > Energy for replicate 30 = *************
*

*> > Energy for replicate 31 = *************
*

*> > Energy for replicate 32 = -543804.4518
*

*> > Total Energy of replicates = *************
*

*> >
*

*> ------------------------------------------------------------------------------
*

*>
*

*> >
*

*> >
*

*> >
*

*> > Output2:
*

*> >
*

*> > Here is the input file:
*

*> > &cntrl
*

*> > imin = 0, irest = 0,
*

*> > ntc=1, ntf=1,
*

*> > ntpr=1000, ntwx=10000,
*

*> > ntb = 0, cut = 999.0, rgbmax=999.0,
*

*> > igb = 1, saltcon=0.2,
*

*> > nstlim = 1000000, nscm=0,
*

*> > dt = 0.0005, ig=-1,
*

*> > ntt = 3, gamma_ln=1000.0,
*

*> > tempi=0.0, temp0=300.0,
*

*> > tgtfitmask=":1-1618.CA",
*

*> > tgtrmsmask=":1-1618",
*

*> > ineb = 1,skmin = 10,skmax = 10,
*

*> > nmropt=1,
*

*> > /
*

*> > &wt type='TEMP0', istep1=0,istep2=800000,
*

*> > value1=0.0, value2=300.0
*

*> > /
*

*> > &wt type='END'
*

*> > /
*

*> >
*

*> >
*

*> >
*

*> --------------------------------------------------------------------------------
*

*>
*

*> >
*

*> > 4. RESULTS
*

*> >
*

*> --------------------------------------------------------------------------------
*

*>
*

*> >
*

*> >
*

*> > The following selection will be used for NEB structure fitting
*

*> > Mask ":1-1618.CA" matches 1618 atoms
*

*> > The following selection will be used for NEB force application
*

*> > Mask ":1-1618" matches 25494 atoms
*

*> >
*

*> > Last atom in NEB fitmask or rmsmask is 25494
*

*> >
*

*> > NSTEP = 0 TIME(PS) = 0.000 TEMP(K) = 0.00 PRESS = 0.0
*

*> > Etot = -47074.9209 EKtot = 0.0000 EPtot = -47074.9209
*

*> > BOND = 970.8273 ANGLE = 3662.2135 DIHED = 19095.3704
*

*> > 1-4 NB = 5347.5040 1-4 EEL = 70022.7257 VDWAALS = -12763.4042
*

*> > EELEC = -116272.6746 EGB = -17137.4828 RESTRAINT = 0.0000
*

*> > NEB replicate breakdown:
*

*> > Energy for replicate 1 = -47074.9209
*

*> > Energy for replicate 2 = -47074.9209
*

*> > Energy for replicate 3 = -47074.9209
*

*> > Energy for replicate 4 = -47074.9209
*

*> > Energy for replicate 5 = -47074.9209
*

*> > Energy for replicate 6 = -47074.9209
*

*> > Energy for replicate 7 = -47074.9209
*

*> > Energy for replicate 8 = -47074.9209
*

*> > Energy for replicate 9 = -47074.9209
*

*> > Energy for replicate 10 = -47074.9209
*

*> > Energy for replicate 11 = -47074.9209
*

*> > Energy for replicate 12 = -47074.9209
*

*> > Energy for replicate 13 = -47074.9209
*

*> > Energy for replicate 14 = -47074.9209
*

*> > Energy for replicate 15 = -47074.9209
*

*> > Energy for replicate 16 = -47074.9209
*

*> > Energy for replicate 17 = -47224.1291
*

*> > Energy for replicate 18 = -47224.1291
*

*> > Energy for replicate 19 = -47224.1291
*

*> > Energy for replicate 20 = -47224.1291
*

*> > Energy for replicate 21 = -47224.1291
*

*> > Energy for replicate 22 = -47224.1291
*

*> > Energy for replicate 23 = -47224.1291
*

*> > Energy for replicate 24 = -47224.1291
*

*> > Energy for replicate 25 = -47224.1291
*

*> > Energy for replicate 26 = -47224.1291
*

*> > Energy for replicate 27 = -47224.1291
*

*> > Energy for replicate 28 = -47224.1291
*

*> > Energy for replicate 29 = -47224.1291
*

*> > Energy for replicate 30 = -47224.1291
*

*> > Energy for replicate 31 = -47224.1291
*

*> > Energy for replicate 32 = -47224.1291
*

*> > Total Energy of replicates = -1508784.8001
*

*> >
*

*> ------------------------------------------------------------------------------
*

*>
*

*> >
*

*> >
*

*> > NMR restraints: Bond = 0.000 Angle = 0.000 Torsion = 0.000
*

*> >
*

*> ===============================================================================
*

*>
*

*> >
*

*> >
*

*> > NSTEP = 1000 TIME(PS) = 0.500 TEMP(K) = 0.00 PRESS = 0.0
*

*> > Etot = -47074.9209 EKtot = 0.0000 EPtot = -47074.9209
*

*> > BOND = 970.8273 ANGLE = 3662.2135 DIHED = 19095.3704
*

*> > 1-4 NB = 5347.5040 1-4 EEL = 70022.7257 VDWAALS = -12763.4042
*

*> > EELEC = -116272.6746 EGB = -17137.4828 RESTRAINT = 0.0000
*

*> > NEB replicate breakdown:
*

*> > Energy for replicate 1 = -47074.9209
*

*> > Energy for replicate 2 = -47338.7714
*

*> > Energy for replicate 3 = -47452.8556
*

*> > Energy for replicate 4 = -47523.3896
*

*> > Energy for replicate 5 = -47567.5181
*

*> > Energy for replicate 6 = -47593.6794
*

*> > Energy for replicate 7 = -47607.9944
*

*> > Energy for replicate 8 = -47616.0892
*

*> > Energy for replicate 9 = -47621.0239
*

*> > Energy for replicate 10 = -47623.2967
*

*> > Energy for replicate 11 = -47626.3209
*

*> > Energy for replicate 12 = -47606.0063
*

*> > Energy for replicate 13 = -47301.0893
*

*> > Energy for replicate 14 = -43986.1754
*

*> > Energy for replicate 15 = -9617.2634
*

*> > Energy for replicate 16 = 160468.8020
*

*> > Energy for replicate 17 = 161919.1912
*

*> > Energy for replicate 18 = -8970.7711
*

*> > Energy for replicate 19 = -43988.7678
*

*> > Energy for replicate 20 = -47409.1935
*

*> > Energy for replicate 21 = -47717.8482
*

*> > Energy for replicate 22 = -47741.0225
*

*> > Energy for replicate 23 = -47738.2980
*

*> > Energy for replicate 24 = -47735.4112
*

*> > Energy for replicate 25 = -47732.2131
*

*> > Energy for replicate 26 = -47725.8105
*

*> > Energy for replicate 27 = -47713.8208
*

*> > Energy for replicate 28 = -47691.4394
*

*> > Energy for replicate 29 = -47650.9497
*

*> > Energy for replicate 30 = -47584.8315
*

*> > Energy for replicate 31 = -47474.7247
*

*> > Energy for replicate 32 = -47224.1291
*

*> > Total Energy of replicates = -1020867.6326
*

*> >
*

*> ------------------------------------------------------------------------------
*

*>
*

*> >
*

*> >
*

*> > _______________________________________________
*

*> > AMBER mailing list
*

*> > AMBER.ambermd.org
*

*> > http://lists.ambermd.org/mailman/listinfo/amber
*

*> >
*

*> _______________________________________________
*

*> AMBER mailing list
*

*> AMBER.ambermd.org
*

*> http://lists.ambermd.org/mailman/listinfo/amber
*

*> _______________________________________________
*

*> AMBER mailing list
*

*> AMBER.ambermd.org
*

*> http://lists.ambermd.org/mailman/listinfo/amber
*

*>
*

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Received on Wed Feb 03 2021 - 09:30:03 PST

Date: Wed, 3 Feb 2021 12:17:26 -0500

I agree with Dave, if you aren't familiar with NEB doing such a large

system can be very difficult to debug. I think it's best to start with

something simpler like alanine dipeptide (done in our Bergonzo et al NEB

paper https://onlinelibrary.wiley.com/doi/abs/10.1002/qua.22405 ), or model

systems like those studied by Delaram et al (

https://pubs.acs.org/doi/abs/10.1021/acs.jctc.9b00329; her phd

dissertation is very detailed and is available here

https://ufdc.ufl.edu/UFE0055988/00001).

On Wed, Feb 3, 2021 at 12:02 PM 李明玉 <santaclaus.sjtu.edu.cn> wrote:

_______________________________________________

AMBER mailing list

AMBER.ambermd.org

http://lists.ambermd.org/mailman/listinfo/amber

Received on Wed Feb 03 2021 - 09:30:03 PST

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