Hi Dr. Kausar, If I want the molecule to have all of its nonbonded interactions with the rest of the system (solvent) at each lambda, don't I want to have vdwq option ON for both couple-lambda0 and couple-lambda1?
What I am attempting to do is mutate molecule A to molecule B through the simulation. Best Regards, Dan On Wed, May 3, 2017 at 1:04 AM, Tasneem Kausar <[email protected]> wrote: > In the last line of mdp file couple-lambda0 and couple-lambda1 have the > same vdwq variable. It indicates A and B state of system. So grompp is > complaining about the identical states. > > You can also see the alchemistry.org for detail information about the free > energy calculations. > > On Wed, May 3, 2017 at 2:14 AM, Dan Gil <[email protected]> wrote: > > > Thank you Dr. Lemkul, > > > > Following your advice, I was able to calculate the solvation free energy > of > > two molecules that I am interested in. The results, unfortunately, were > not > > what I expected. I want to try an alternative method, that is, the > > alchemical thermodynamic integration method. > > > > If I understand this correctly, I should be able to calculate the free > > energy difference between two systems A and B as I change the topology of > > the molecule from A to B in small steps. > > > > I wasn't able to find a tutorial online, but I attempted to try the > method > > and I obtained this error from grompp: > > > > WARNING 1 [file grompp.mdp, line 43]: > > The lambda=0 and lambda=1 states for coupling are identical > > > > I was hoping if you could help me understand what I am missing in my > > topology or mdp file. > > > > Topology: > > [ moleculetype ] > > HEPT 3 > > > > [ atoms ] > > 1 opls_135 1 HEPT CH3 1 -0.180 12.011 > > opls_961 0.360 12.011 > > 2 opls_136 1 HEPT CH2 2 -0.120 12.011 > > opls_962 0.240 12.011 > > 3 opls_136 1 HEPT CH2 3 -0.120 12.011 > > opls_962 0.240 12.011 > > 4 opls_136 1 HEPT CH2 4 -0.120 12.011 > > opls_962 0.240 12.011 > > 5 opls_136 1 HEPT CH2 5 -0.120 12.011 > > opls_962 0.240 12.011 > > 6 opls_136 1 HEPT CH2 6 -0.120 12.011 > > opls_962 0.240 12.011 > > 7 opls_135 1 HEPT CH3 7 -0.180 12.011 > > opls_961 0.360 12.011 > > 8 opls_140 1 HEPT H 1 0.060 1.008 > > opls_965 -0.120 18.998 > > 9 opls_140 1 HEPT H 1 0.060 1.008 > > opls_965 -0.120 18.998 > > 10 opls_140 1 HEPT H 1 0.060 1.008 > > opls_965 -0.120 18.998 > > 11 opls_140 1 HEPT H 2 0.060 1.008 > > opls_965 -0.120 18.998 > > 12 opls_140 1 HEPT H 2 0.060 1.008 > > opls_965 -0.120 18.998 > > 13 opls_140 1 HEPT H 3 0.060 1.008 > > opls_965 -0.120 18.998 > > 14 opls_140 1 HEPT H 3 0.060 1.008 > > opls_965 -0.120 18.998 > > 15 opls_140 1 HEPT H 4 0.060 1.008 > > opls_965 -0.120 18.998 > > 16 opls_140 1 HEPT H 4 0.060 1.008 > > opls_965 -0.120 18.998 > > 17 opls_140 1 HEPT H 5 0.060 1.008 > > opls_965 -0.120 18.998 > > 18 opls_140 1 HEPT H 5 0.060 1.008 > > opls_965 -0.120 18.998 > > 19 opls_140 1 HEPT H 6 0.060 1.008 > > opls_965 -0.120 18.998 > > 20 opls_140 1 HEPT H 6 0.060 1.008 > > opls_965 -0.120 18.998 > > 21 opls_140 1 HEPT H 7 0.060 1.008 > > opls_965 -0.120 18.998 > > 22 opls_140 1 HEPT H 7 0.060 1.008 > > opls_965 -0.120 18.998 > > 23 opls_140 1 HEPT H 7 0.060 1.008 > > opls_965 -0.120 18.998 > > ... And so on with the bonds, pairs, angles, and dihedrals directive. > > > > MDP File: > > > > ;Integration Method and Parameters > > integrator = md > > nsteps = 10000 > > dt = 0.002 > > nstenergy = 1000 > > nstlog = 5000 > > > > ;Output Control > > nstxout = 0 > > nstvout = 0 > > > > ;Cutoff Schemes > > cutoff-scheme = group > > rlist = 1.0 > > vdw-type = cut-off > > rvdw = 2.0 > > > > ;Coulomb interactions > > coulombtype = pme > > rcoulomb = 1.0 > > fourierspacing = 0.4 > > > > ;Constraints > > constraints = all-bonds > > > > ;Temperature coupling > > tcoupl = v-rescale > > tc-grps = system > > tau-t = 0.1 > > ref-t = 300 > > > > ;Pressure coupling > > pcoupl = parrinello-rahman > > ref-p = 1.01325 > > compressibility = 4.5e-5 > > tau-p = 5 > > > > ;Free energy calculation > > free-energy = yes > > init-lambda = 0 > > delta-lambda = 0.00001 > > couple-moltype = HEPT > > couple-lambda0 = vdwq > > couple-lambda1 = vdwq > > > > On Mon, Apr 3, 2017 at 2:05 PM, Justin Lemkul <[email protected]> wrote: > > > > > > > > > > > On 4/3/17 2:01 PM, Dan Gil wrote: > > > > > >> Thank you Dr. Lemkul, > > >> > > >> I am trying to run grompp with the md integrator, but I am getting > this > > >> error: > > >> "For proper sampling of the (nearly) decoupled state, stochastic > > dynamics > > >> should be used" > > >> > > >> Should I ignore this warning with the -maxwarn option and try running > > it? > > >> I > > >> will see if I obtain comparable values for ethanol. > > >> > > >> > > > People have already done such a comparison and that's why grompp is > > > telling you this - it's better to use the Langevin integrator. You'll > > get > > > better sampling, particularly towards the end states. Using -maxwarn > > tells > > > grompp "you're trying to prevent me from making a mistake, but I want > to > > do > > > it anyway" :) You'd better have a really, really good reason to try to > > > override it. > > > > > > -Justin > > > > > > > > > Best Regards, > > >> > > >> Dan > > >> > > >> > > >> On Mon, Mar 27, 2017 at 12:51 PM, Justin Lemkul <[email protected]> > > wrote: > > >> > > >> > > >>> > > >>> On 3/26/17 9:40 PM, Dan Gil wrote: > > >>> > > >>> Hi, > > >>>> > > >>>> I am following Dr. Sander Pronk's and Dr. Justin Lemkul's tutorial > on > > >>>> calculating free energy of solvation. Is it possible and > theoretically > > >>>> sound to use the md integrator instead of the sd integrator for > these > > >>>> calculations? > > >>>> > > >>>> > > >>>> Langevin dynamics gives better sampling so it is frequently used for > > >>> free > > >>> energy calculations. You may get comparable results with the > leap-frog > > >>> integrator, but I haven never done a side-by-side comparison. > > >>> > > >>> -Justin > > >>> > > >>> I have already done a considerable amount of work using md > integration, > > >>> and > > >>> > > >>>> I want to make sure that the free energy values I calculate are > > >>>> consistent > > >>>> with my previous work. > > >>>> > > >>>> If using the md integrator is not sound, is there an alternative way > > of > > >>>> calculating solvation energy that will be consistent? > > >>>> > > >>>> Best Regards, > > >>>> > > >>>> Dan > > >>>> > > >>>> > > >>>> -- > > >>> ================================================== > > >>> > > >>> 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 > > >>> > > >>> [email protected] | (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 [email protected]. > > >>> > > >>> > > > -- > > > ================================================== > > > > > > 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 > > > > > > [email protected] | (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 [email protected]. > > > > > -- > > 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 [email protected]. > > > -- > 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 [email protected]. > -- 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 [email protected].
