For decharge step you generally want your endstates to be:
Lambda 0: Molecule with charge
Lambda 1.0: Molecule without charge
Therefore you'd want 2 copies of your ligand.
So you'd want
Timask1=':BG6', timask2=':BG7' (or whatever second copy of your ligand is)
crgmask=':BG7'
On 10/10/19, 8:16 AM, "Sadaf Rani" <sadafrani6.gmail.com> wrote:
CAUTION: EXTERNAL EMAIL
Dear Amber and Charlie
I run TI calculation for calculating absolute free energy calculation of
ligand with the following input in decharge step:-
icfe = 1, clambda = 0.0, scalpha = 0.5, scbeta = 12.0,
logdvdl = 1,
ifmbar = 1, mbar_states= 11,
mbar_lambda= 0.0, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0
bar_intervall = 10,
timask1 = ':BG6', timask2 = '',
ifsc = 0, crgmask = ':BG6',
but it gives me following error:-
TI Mask 1 :BG6; matches 27 atoms
TI Mask 2 matches 0 atoms
TI region 1: 8591 atoms
TI region 2: 8564 atoms
Removing charge of -0.6555 from atom 1
Removing charge of 0.4043 from atom 2
Removing charge of 0.1047 from atom 3
Removing charge of 0.0443 from atom 4
Removing charge of 0.2450 from atom 5
Removing charge of -0.7348 from atom 6
Removing charge of 0.4283 from atom 7
Removing charge of -0.0045 from atom 8
Removing charge of 0.2380 from atom 9
Removing charge of -0.7107 from atom 10
Removing charge of 0.4056 from atom 11
Removing charge of 0.0704 from atom 12
Removing charge of 0.5188 from atom 13
Removing charge of -0.7055 from atom 14
Removing charge of 0.4528 from atom 15
Removing charge of -0.0204 from atom 16
Removing charge of -0.5253 from atom 17
Removing charge of 0.2104 from atom 18
Removing charge of 0.0424 from atom 19
Removing charge of 0.2913 from atom 20
Removing charge of -0.0024 from atom 21
Removing charge of -0.0024 from atom 22
Removing charge of -0.5859 from atom 23
Removing charge of 1.3045 from atom 24
Removing charge of -0.9377 from atom 25
Removing charge of -0.9377 from atom 26
Removing charge of -0.9377 from atom 27
Total charge of -2.00000000 removed from 27 atoms
MBAR - lambda values considered:
11 total: 0.0000 0.1000 0.2000 0.3000 0.4000 0.5000 0.6000 0.7000
0.8000 0.9000 1.0000
Extra energies will be computed 10000 times.
Checking for mismatched coordinates.
ERROR: timask1/2 must match the same number of atoms for non-softcore
run
how should I set input to fix this error
Looking forward to hearing from you.
thank you
Sadaf
On Thu, Oct 3, 2019 at 5:13 PM Charles Lin <Charles.lin.silicontx.com>
wrote:
> You essentially just need to run your production scheme with different
> lambdas by changing the clambda value.
>
> 0.0 = your ligand fully exists
> 1.0 = your ligand has fully disappeared.
>
> Follow the folder setup like this:
> http://ambermd.org/tutorials/advanced/tutorial9/index.html
>
> You may want to increase the number of lambda windows you're using because
> your transformation is a lot bigger when you're augmenting both
> electrostatics and vdws. You may want to considering doing it in two steps
> where you first decharge your molecule then disappear the vdws. (Similar
> to the tutorial except scmask2 and timask2 are both '', and you don't run a
> recharge window.
>
> -Charlie
>
> On 10/3/19, 11:06 AM, "Sadaf Rani" <sadafrani6.gmail.com> wrote:
>
>
> CAUTION: EXTERNAL EMAIL
>
>
>
> Dear Amber
> I am also looking for the same.
> I have a ligand for my protein for which I want to calculate absolute
> binding energy; in which I want the ligand to disappear completely at
> the
> start and then appear with all vander waals and electrostatic
> interactions.
> As per my understanding(I may be wrong in it), I should set up my
> ligand
> in solution and complex in solution as per the following input:-
> Minimization:-
> &cntrl
> imin = 1, ntmin = 2,
> maxcyc = 1000,
> ntpr = 200, ntwe = 200,
> ntb = 1,
> ntr = 1, restraint_wt = 5.00,
> restraintmask='!:WAT & !.H=',
>
> icfe = 1, ifsc = 1, clambda = 0.0, scalpha = 0.5, scbeta = 12.0,
> logdvdl = 0,
> timask1=':1', scmask1=':1',
> timask2='', scmask2='',
> /
> &ewald
> /
>
> Heating:-
> &cntrl
> imin = 0, nstlim = 10000, irest = 0, ntx = 1, dt = 0.002,
> nmropt = 1,
> ntt = 1, temp0 = 300.0, tempi = 5.0, tautp = 1.0,
> ntb = 1,
> ntc = 2, ntf = 1,
> ioutfm = 1, iwrap = 1,
> ntwe = 1000, ntwx = 1000, ntpr = 1000, ntwr = 5000,
>
> ntr = 1, restraint_wt = 5.00,
> restraintmask='!:WAT & !.H=',
>
> icfe = 1, ifsc = 1, clambda = 0.5, scalpha = 0.5, scbeta = 12.0,
> logdvdl = 0,
> timask1=':1', scmask1=':1',
> timask2='', scmask2='',
> /
> &ewald
> /
>
> &wt
> type='TEMP0',
> istep1 = 0, istep2 = 8000,
> value1 = 5.0, value2 = 300.0
> /
>
> &wt type = 'END'
> /
>
> Pressurizing:-
> &cntrl
> imin = 0, nstlim = 10000, irest = 1, ntx = 5, dt = 0.002,
> ntt = 1, temp0 = 300.0, tautp = 1.0,
> ntp = 1, pres0 = 1.0, taup = 2.0,
> ntb = 2,
> ntc = 2, ntf = 1,
> ioutfm = 1, iwrap = 1,
> ntwe = 1000, ntwx = 1000, ntpr = 1000, ntwr = 5000,
>
> ntr = 1, restraint_wt = 5.00,
> restraintmask='!:WAT & !.H=',
>
> icfe = 1, ifsc = 1, clambda = 0.5, scalpha = 0.5, scbeta = 12.0,
> logdvdl = 0,
> timask1=':1', scmask1=':1',
> timask2='', scmask2='',
> /
> &ewald
> /
> What next? How to set input for absolute free energy calculations in
> order
> to disappear ligand and slowly appear with increase in lambda?
>
> Looking for your kind suggestions, please.
>
> Thank you
>
>
> On Wed, Oct 2, 2019 at 4:20 PM Charles Lin <Charles.lin.silicontx.com>
> wrote:
>
> > Hi,
> >
> > I'd follow mostly the same protocol as a relative binding free energy
> > (where ligand a transforms to ligand b), but instead of having a
> ligand b,
> > your timask, scmask of those regions becomes nothing
> > timask2='', scmask2='',
> >
> > I would also apply the virtual bond algorithm described here to keep
> your
> > ligand in the pocket (described as a virtual bond here)
> > https://pubs.acs.org/doi/pdf/10.1021/jp505777n
> >
> > These calculations are fairly expensive to calculate. Relative
> binding
> > free energies converge a lot more quickly because the amount of
> phase space
> > to sample is already somewhat more limited due to the presence of a
> ligand
> > you already know its binding pose/pocket position. The less data
> you know
> > about your system, the less likely you'll place your ligand
> correctly, and
> > simple changes such as having a side chain incorrect, could vastly
> give
> > different absolute binding free energy values.
> >
> > -Charlie
> >
> > On 10/1/19, 4:26 PM, "Debarati DasGupta" <
> debarati_dasgupta.hotmail.com>
> > wrote:
> >
> >
> > CAUTION: EXTERNAL EMAIL
> >
> >
> >
> > Dear All,
> >
> > I have been trying to read more about free energy calculations
> using
> > TI method implemented in AMBER18. I recently did a webinar by CCG
> group
> > wherein in MOE2019 they have incorporated the TI implementation setup
> > collaborating with AMBER.
> >
> > I did read this publication too from Professor Carlos
> Simmerling’s
> > webpage “
> >
> https://chemrxiv.org/articles/Blinded_Prediction_of_Protein-Ligand_Binding_Affinity_Using_Amber_Thermodynamic_Integration_for_the_2018_D3R_Grand_Challenge_4/8312375/1
> > ”
> > This did throw a lot of light on how to exactly setup TI
> calculations
> > in AMBER.
> >
> > I still have a very fundamental question, it may be very stupid,
> but I
> > am not sure how to setup TI to calculate the absolute binding
> affinity of a
> > ligand towards a protein.
> > Is there something I am missing totally?
> > My protein of interest is ABL-kinase and I have a done some
> co-solvent
> > simulations to get some hotspots( areas of possible ligandibility);
> I need
> > to calculate the binding affinity of these small cosolvents towards
> ABL.
> > TI methods give us a “deldelG”, which is relative binding
> affinity, if
> > we have a receptor (say CathepsinS) and have a set of 10+ ligands
> with a
> > common core (scaffold).
> > If I have one protein +1 ligand and I need to calculate the
> binding
> > affinity what is the procedure to be adopted?
> > Is there a tutorial to do that?
> >
> > I am not looking to do MMGBSA/PBSA on this system.
> >
> > Thanks
> >
> > _______________________________________________
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Received on Thu Oct 10 2019 - 06:30:03 PDT
