Hi Abir,
Thanks for the quick reply. Here is the link to download the coordinates and input parameters for equilibration for runing the TI. I first run tleap and then paramd to reduce the system size. The coordinates are the finals used for equilibration.
Let me know if you need more information. Just let you know, I also finished test SSC runs for additional mutations in another protein system, the results seem reasonable. But this one is not good.
Best,
Zizhang
https://drive.google.com/drive/folders/1mUhsKSG6zSEHM2DbMnQwt52UpXZQQH6y?usp=sharing <
https://drive.google.com/drive/folders/1mUhsKSG6zSEHM2DbMnQwt52UpXZQQH6y?usp=sharing>
> On Apr 26, 2021, at 8:19 AM, Abir Ganguly <abir.ganguly.rutgers.edu> wrote:
>
>
> Hi Zizhang,
>
> Could you please provide us with some more information so that we can try and reproduce the result and investigate the source of the error? I see you have provided the input file. Could you also perhaps send us the starting pdb/parm rst files and the tleap input file that you used to build the system?
>
> thanks,
>
> Abir Ganguly, Ph.D.
> Assistant Research Professor
> Institute for Quantitative Biomedicine (IQB)
> Rutgers, The State University of New Jersey
> 174 Frelinghuysen Road
> Piscataway, NJ 08854 USA
>
> From: zz sheng <shengzizhang.gmail.com>
> Sent: Sunday, April 25, 2021 11:32 PM
> To: AMBER Mailing List <amber.ambermd.org>
> Subject: [AMBER] TI free energy calculation issue after applying smoothstep in Amber20
>
> Hi All,
>
> I applied the smoothstep (gti_lam_sch = 1, smoothstep2, ) in Amber20 to calculate the free energy change between two proteins upon an amino acid residue mutation. I wished to improve the predictions, but I found that the predicted ddG has huge difference to the experimental ddG (>10kcal/mol), while the TI without smoothstep is reasonably good. I used 13 gaussian lambda windows suggested in the manual.
>
> My questions are:
> 1. should the same gaussian weighted dG calculation method in the Amber20 manual used for both TI runs with and without the smoothstep or has to adjust someway for the smoothstep TI run?
> 2. Is the current smoothstep in premed.cuda is good for protein residue mutations? I tested multiple protein complex systems, the predicted ddGs with smoothstep applied consistently showed very big deviation from the experimental ddG but the TI prediction without the smoothstep have much smaller deviation from the experimental ddGs.
> 3. What is the potential causes for the failure of TI with smoothstep?
>
> I attached the plots for dU/dL and the production run script.
>
> Thanks,
>
> Best,
>
> Zizhang Sheng
>
> &cntrl
> ntx = 5,
> irest = 0,
> ntpr = 50000,
> ntwx = 0,
> ntwr = 100000,
> ntwe = 0,
>
> ntf = 1,
> ntb = 1,
> cut = 9.0,
>
> nstlim = 1000000,
> nscm = 0,
> t = 0.0,
> dt = 0.001,
> iwrap = 1,
>
> temp0 = 300.0,
> tempi = 300.0,
> ntt = 1,
> tautp = 2.0,
>
> ntc = 1,
> tol = 0.000001,
>
> icfe = 1,
> ifsc=1,
> clambda = 0.99078,
> scalpha = 0.2,
> scbeta = 50.0,
> gti_lam_sch = 1,
> logdvdl = 0,
> timask1 = ':91',
>
> timask2 = ':110',
>
> scmask1 = ':91 & !.N,C,O,CA,H,HA',
> scmask2 = ':110 & !.N,C,O,CA,H,HA',
> &end
> #############
> Receptor alone dU/dL with SSC
> 0.0 28.461845988470817 0 0
> 0.00922 41.5202134382 0.781668096672 7.81668096672
> 0.04794 48.8885711107 0.971343880807 9.71343880807
> 0.11505 68.0280780991 1.67078999671 16.7078999671
> 0.20634 24.5277876556 1.31925135067 13.1925135067
> 0.31608 -31.7344411295 1.1050460433 11.050460433
> 0.43738 -69.773583749 1.20482865975 12.0482865975
> 0.5 -82.1982043524 1.04939990253 10.4939990253
> 0.56262 -97.1059946206 1.28429193452 12.8429193452
> 0.68392 -116.569613146 1.73873480821 17.3873480821
> 0.79366 -172.374025406 2.91814470302 29.1814470302
> 0.88495 -204.589793294 2.37335608886 23.7335608886
> 0.95206 -90.095173025 1.2019919667 12.019919667
> 0.99078 -33.482114292 0.575018447317 5.75018447317
> 1.0 9.661007606978377 0 0
> ('# dG =', -65.11406211283327)
>
> ###############
> Complex dU/dL with SSC
>
> 0.0 29.66806951796594 0 0
> 0.00922 45.544092324 0.722305149907 7.22305149907
> 0.04794 57.5255406441 0.863067824535 8.63067824535
> 0.11505 87.9760434649 1.53169722946 15.3169722946
> 0.20634 31.3018672598 1.18211280542 11.8211280542
> 0.31608 -25.1897950745 1.22934451619 12.2934451619
> 0.43738 -64.0742065629 0.978913035021 9.78913035021
> 0.5 -78.4106044067 1.16028175003 11.6028175003
> 0.56262 -88.0902537712 1.24147706307 12.4147706307
> 0.68392 -97.7829897345 1.47389749675 14.7389749675
> 0.79366 -138.81691062 2.42538220771 24.2538220771
> 0.88495 -173.068723519 2.50731699029 25.0731699029
> 0.95206 -85.7638677763 1.04041722421 10.4041722421
> 0.99078 -40.7675065699 0.636340624466 6.36340624466
> 1.0 -6.8073131443268196 0 0
> ('# dG =', -51.929494997797704)
>
> ddG from experiment: 1.36Kcal/mol, ddG without SSC: 1.14Kcal/mol.
>
>
>
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Received on Mon Apr 26 2021 - 08:00:02 PDT
