On 6/12/17 5:44 PM, Varvdekar Bhagyesh Rajendra wrote:
Dear Justin,
So if I am interpreting it correct, it is reasonable if sc-coul = no even when
partial coulomb interpolation takes place during transition from couple-lambda0
= none to couple-lambda1 = vdw-q , right?
Yes. But again I must emphasize that your approach to treating a peptide is
going to fraught with problems. This is not an effective way to get a binding
free energy.
-Justin
Thank you for the reply,
-
Bhagyesh
----- Original Message -----
From: "Justin Lemkul" <jalem...@vt.edu>
To: gmx-us...@gromacs.org
Sent: Tuesday, June 13, 2017 2:18:30 AM
Subject: Re: [gmx-users] Doubt about Free Energy Calculations using g_bar
On 6/12/17 11:47 AM, Varvdekar Bhagyesh Rajendra wrote:
Dear Justin,
I have compiled the following free energy code for use in the g_bar program for
finding Binding affinity of a Protein-ligand complex, with ligand being a
peptide. I would appreciate if you could please verify it's correctness and
perhaps suggest any valuable improvements, if deemed necessary.
I am not sure about the input in the parameters for: *sc-coul* and
*couple-intramol* though.
Since couple-lambda0 = none and couple-lambda1 = vdw-q, I assume coulomb
interpolation must be taking place, and sc-coul should be *yes*.
Not necessarily. Scaling Coulombic interactions linearly is what is more
commonly done.
Also, as my ligand is a peptide, I presume couple-intramol should also be *yes*.
If you're dealing with a peptide, you shouldn't be doing an alchemical
transformation. It will probably never converge. PMF or MM/PBSA are much
better approaches for determining binding free energies for these types of
systems.
-Justin
; Free energy control
free_energy = yes
init_lambda_state = 0
delta_lambda = 0
calc_lambda_neighbors = 1 ; only immediate neighboring windows
; Vectors of lambda specified here
; Each combination is an index that is retrieved from init_lambda_state for
each simulation
; init_lambda_state 0 1 2 3 4 5 6 7 8 9 10
11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26
27 28 29 30 31 32 33 34 35 36 37 38 39 40
vdw_lambdas = 0.00 0.05 0.10 0.15 0.20 0.25 0.30 0.35 0.40 0.45
0.50 0.55 0.60 0.65 0.70 0.75 0.80 0.85 0.90 0.95 1.00 1.00 1.00 1.00 1.00 1.00
1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00
coul_lambdas = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.05 0.10 0.15 0.20 0.25
0.30 0.35 0.40 0.45 0.50 0.55 0.60 0.65 0.70 0.75 0.80 0.85 0.90 0.95 1.00
; We are not transforming any bonded or restrained interactions
bonded_lambdas = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
restraint_lambdas = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
mass_lambdas = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
temperature_lambdas = 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
; Options for the decoupling
sc-alpha = 0.5
sc-coul = ?? ; As linear interpolation of Coulomb takes
place, I suppose it should be *yes*
sc-power = 1.0
sc-sigma = 0.3
couple-moltype = Protein_chain_B ; name of moleculetype to
decouple
couple-lambda0 = none ; interactions are turned off in the
beginning
couple-lambda1 = vdw-q ; all interactions are on in the end
couple-intramol = ?? ; since my ligand is a peptide, I suppose
the intramol interactions should be *yes*
nstdhdl = 10
Thanking in anticipation,
Best Regards,
Bhagyesh
----- Original Message -----
From: "Justin Lemkul" <jalem...@vt.edu>
To: gmx-us...@gromacs.org
Sent: Sunday, June 11, 2017 7:01:26 AM
Subject: Re: [gmx-users] Doubt about Free Energy Calculations using g_bar
On 6/10/17 6:15 AM, Varvdekar Bhagyesh Rajendra wrote:
Dear Justin,
Just so we are on the same page, this means that if I don't touch the topology
file and use the following mdp snippet, charges *are present* in the topology
file for the ligand group and they are automatically set to zero while turning
on vdW interactions (from 0 to 1) right ? Hence, there is no need to manually
set charges to zero (The old style of doing the calculations), right?.
Yes. You can easily confirm this using energygrps between your transformed
molecule and the rest of the system. Coul-SR should be zero.
Then the charges too, are turned off from 0 to 1? (1 state being the actual
charges present in the topology file).
Charges are turned *on* if they are defined as off in the A-state (lambda=0) and
on in the B-state (lambda=1).
-Justin
--
==================================================
Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow
Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201
jalem...@outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul
==================================================
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