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?
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 ================================================== -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists * For (un)subscribe requests visit https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-requ...@gromacs.org. -- Gromacs Users mailing list * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting! * Can't post? 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