Hi Fabricio,
Can you clarify what exactly you mean by "start with the TI simulation"?
What values of lambda? Does this behavior occur for all of them?
Some other things that might be informative: What topolog(y/ies) are you
using? What bonded terms exist on the protons?
I believe the best established QM/MM protocols for pKa type calculations
involve some kind of restraints, but how you choose to apply them is still
something of an art. The following paper describes a protocol in CHARMM,
but I'm pretty sure the ideas transfer well to AMBER:
Li and Qiang, J Phys Chem B 2003, 107, 14521.
I attempted similar calculations a while back but had a very difficult time
getting reproducible results. I suspect that there are some zero of energy
issues that need to be handled when you have the same number of electrons
but different orbitals. I am not sure what the solution is there. An
alternative path is to perform the proton disappearing as an MM to MM
mutation and then perform MM to QM/MM transformations on the endpoints as a
kind of correction. This is more work but I suspect will converge faster in
most situations.
Regards,
Brian
On Sat, Feb 2, 2013 at 2:35 PM, Fabrício Bracht <bracht.iq.ufrj.br> wrote:
> Hi all. I am doing a TI caltulation in order to obtain the free energy
> values associated with the loss of a proton from a hydroxyl group bound to
> a zinc atom coordinated with 3 other aminoacids. System 1 comprises of a
> water molecule bound to the zinc atom, and system 2 is the hydroxyl group.
> When I run qmmm simulations, using DFTB, of both systems separately, the
> system stays intact, i.e. no bonds are broken and both the water and the
> hydroxyl stay bound to the zinc atom ( as was expected). But as soon as I
> star with the TI simulation, the hydroxyl group always drifts away.
> Sometimes the oxygen atom stays and the hydrogen goes for a walk. This
> happens only on TI simulations and the water system stays intact. I have
> tried different sizes of qm region, different cutoffs, tried several
> different starting structures ( minimized, equilibrated, thermalized etc)
> and the result is almost always the same. Below is the input file for the
> hydroxyl group system. I thought about restraining the hydroxyl group using
> the nmropt module. Can I use the dvdl_norest flag to ignore those
> restraints in the energy calculation? Please let me know if you need any
> other detail from the simulation and/or if you need/want any file from the
> inputs.
> Thank you
> Fabrício Bracht
>
> TI of hydroxyl group step 1
> &cntrl
> imin = 0,
> irest = 1,
> ntx = 7,
> ntb = 2, pres0 = 1.0, ntp = 1, taup = 2.0,
> cut = 8.0,
> ntr = 0,
> ntc = 2,
> ntf = 1,
> temp0 = 298.0,
> ntt = 3,
> gamma_ln = 1.0,
> nstlim = 1000000, dt = 0.0005, ntave = 100,
> ntpr = 100, ntwx = 100, ntwr = 100,
> ig = 10703, ioutfm = 1, iwrap = 1,
> icfe = 1, ifsc = 1, clambda = 0.01592,
> ifqnt = 1, scmask = ':342', idecomp = 0, nmropt = 0,
> /
> &qmmm
> qmmask=
> ':200,255,258&!.CA,C,HA,O,N,HN,H|:341,342|(:202,204&!.CA,C,HA,O,N,H)'
> dftb_3rd_order = 'PA'
> qmcharge=-1,
> qm_theory='DFTB',
> qmshake=0,
> qm_ewald=1, qm_pme=1
> qmcut=9.0
> writepdb=1
> /
> Receptor residues
> RRES 1 7853
> END
> Printing
> RES 1 342
> END
> END
> _______________________________________________
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> http://lists.ambermd.org/mailman/listinfo/amber
>
--
================================ Current Address =======================
Brian Radak : BioMaPS
Institute for Quantitative Biology
PhD candidate - York Research Group : Rutgers, The State
University of New Jersey
University of Minnesota - Twin Cities : Center for Integrative
Proteomics Room 308
Graduate Program in Chemical Physics : 174 Frelinghuysen Road,
Department of Chemistry : Piscataway, NJ
08854-8066
radak004.umn.edu :
radakb.biomaps.rutgers.edu
====================================================================
Sorry for the multiple e-mail addresses, just use the institute appropriate
address.
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Received on Sat Feb 02 2013 - 13:30:02 PST
