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
> >
> ------------------------------------------------------------------------------
>
> >
> >
> > _______________________________________________
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> > http://lists.ambermd.org/mailman/listinfo/amber
> >
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Received on Wed Feb 03 2021 - 09:30:03 PST
