Re: [gmx-users] Gromos54a7 electrostatics interactions ?
Hi, I tried to reply yesterday, but apparently my message was too big to be sent (probably because I replied within your own reply ?). I try a second time: Thanks for checking! Exactly, this temperature is for sure above the phase transition temperature of the lipid I'm studying. Except for the potential use of sterols discussed further, I will only use PC lipids. However, some of my molecules do have an alkyl chain. One point of using gromos54a7 is that those alkyl chains will interact with PC's alkyl chains as PC's alkyl chains interact between each other. What I mean is that atomtypes used for both lipids and molecules' alkyl chains will be identical (CH2, CH3...). Berger lipids use different atomtypes for the alkyl chains (LP2, LP3...). >From what I think I know, Berger lipids is pretty compatible with gromos' forcefields. So my first intention was to use berger lipids' PC together with gromos53a6's molecules. However, it might be better to change the atomtypes from the alkyl chains of my molecules so that they match the berger lipids alkyl chains atomtypes. It seems that they did so in this paper http://pubs.acs.org/doi/abs/10.1021/jp501622d I would be very interested in getting your opinion about this. About the removal of leaflets COM movements, I'm not sure to know how to do that ? "Simply" with trjconv ? I also think that Berger setup will give the fastest simulations! Thanks for the info about the condensing effect of Holtje sterol on berger lipids. Still not sure if I will run simulations with sterols but this will for sure be taken into account whenever needed. I used a shortcut, but it is true that I should try to understand why both forcefields don't give similar results (if it is the case). Thanks for your clear and detailed reply ! -- 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.
Re: [gmx-users] Gromos54a7 electrostatics interactions ?
Thanks again for your reply and all the info that I've read with great interest! I would like to simulate lipid bilayers that contain my molecules and have a look at my molecules' location and orientation as well as how they can affect lipids properties. My plan would be to try two different forcefields: Gromos54a7 and Berger lipids. For gromos54a7, I would use a mdp file (for run production) like this one: "integrator = md nsteps = 12500 dt = 0.002 nstxout = 50 nstvout = 50 nstxtcout = 1 nstenergy = 1000 nstlog = 1000 continuation= yes constraint_algorithm = lincs constraints = all-bonds lincs_iter = 1 lincs_order = 4 ns_type = grid nstlist = 5 nstcalclr = 1 vdw-type= cut-off rlist = 0.8 rcoulomb= 1.4 rvdw= 1.4 coulombtype = reaction-field epsilon-rf = 62 tcoupl = Nose-Hoover tc-grps = MOLECULE_LIPID SOL tau_t = 0.5 0.5 ref_t = 298 298 pcoupl = Parrinello-Rahman pcoupltype = semiisotropic tau_p = 2.0 ref_p = 1.0 1.0 compressibility = 4.5e-54.5e-5 pbc = xyz DispCorr= No gen_vel = no nstcomm = 1 comm-mode = Linear comm-grps = MOLECULE_LIPID SOL cutoff-scheme= group" Berger lipids simulations would be performed with similar mdp options, except for a few parameters, namely: "integrator = md nsteps = 12500 dt = 0.002 nstxout = 50 nstvout = 50 nstxtcout = 1 nstenergy = 1000 nstlog = 1000 continuation= yes constraint_algorithm = lincs constraints = all-bonds lincs_iter = 1 lincs_order = 4 ns_type = grid nstlist = 5 rlist = 1.0 rcoulomb= 1.0 rvdw= 1.0 coulombtype = PME pme_order = 4 fourierspacing = 0.12 tcoupl = Nose-Hoover tc-grps = MOLECULE_LIPID SOL tau_t = 0.5 0.5 ref_t = 298 298 pcoupl = Parrinello-Rahman pcoupltype = semiisotropic tau_p = 2.0 ref_p = 1.0 1.0 compressibility = 4.5e-54.5e-5 pbc = xyz DispCorr= EnerPres gen_vel = no nstcomm = 1 comm-mode = Linear comm-grps = MOLECULE_LIPID SOL cutoff-scheme = Verlet" I would do one repetition of each system with each forcefield. Then I would compare the results between each other and with experimental results. Hopefully, both forcefields would give similar results and would be in good agreement with experimental results, I would then perform two more repetitions with the faster setup. If both forcefields don't give similar results, then I would select the one that is in better agreement with experimental results (hopefully there would be at least one huhu). The forcefield choice is also guided by the possibility of adding some lipids (sterols...) if useful (depending on experimental results). With gromos54a7 I would use sterol topology available on ATB and for Berger lipids I would start from sterol topology from Höltje et al.. I have for sure to make my own opinion about the different forcefields. However, I am lucid enough to understand that some people are much more experienced and qualified than I am. I hope I will have the opportunity to progress, and I would not blindly follow anyone's opinion though. But I don't think Mark Abraham's opinion and yours are 'anyone's opinion', so I carefully read your posts :) Thanks! 2017-09-22 20:37 GMT+02:00 Thomas Piggot : > > > On 22/09/17 16:59, Sim gmx wrote: > >> First of all, thanks for your replies! >> >> 1) Indeed, both epsilon-r and epsilon-rf are such constants. However, in >> the paper I guess that they refer to the relative dielectric constant of >> the reaction field, i.e. epsilon-rf. Or do I miss something ? >> > Yes, they are referring to epsilon-rf. > >> 2) I will for sure contact them to collect all these info if I go further >> with this forcefield! >> > I've tested things pretty extensively with this force field so I don't > think you need to contact them. If you post your mdp it will make things > much easier as we can see exactly what you're are doing and can let you > know if there is anything that doesn't look correct. > >> >> 3) I don't think I understand everything there. What I think I get is: >> using a verlet scheme with parameters that were not initially designed for >> this scheme is risky and should be carefully assessed. >> > This is what I was saying I have already assessed and, for DPPC at least, > the membrane does not behave well with Verlet and reaction-field. If
Re: [gmx-users] Gromos54a7 electrostatics interactions ?
First of all, thanks for your replies! 1) Indeed, both epsilon-r and epsilon-rf are such constants. However, in the paper I guess that they refer to the relative dielectric constant of the reaction field, i.e. epsilon-rf. Or do I miss something ? 2) I will for sure contact them to collect all these info if I go further with this forcefield! 3) I don't think I understand everything there. What I think I get is: using a verlet scheme with parameters that were not initially designed for this scheme is risky and should be carefully assessed. Plus, parameters used by Poger are very likely to be incompatible with verlet scheme. >From this, I conclude it's not even worth giving it a try. So my options are: - use a group scheme, that will be slower - use a different force field, but which one since I do have the topologies of my small molecules for gromos 53a6/54a7 ? Would Berger Lipids be a good option here ? About Tom's reply: 1. That's good to know, especially as it does not appear anywhere in the original papers. 2. Is using a setup with all cutoffs = 1.4 more "adequate" than the twin-range setup then ? Or is it just a "good to know" stuff ? I would naturally use the fastest correct setup which seems to be the twin-range one (with group-scheme), am I wrong ? Again, thanks to both of you. 2017-09-22 14:29 GMT+02:00 Piggot T. : > Hi, > > In addition to Mark's comments, there are a few other points to be aware > of: > > 1. If you use the twin-range scheme (i.e. 0.8/1.4) with nstlist 5, you > need to set nstcalclr to 1 to get results matching those as reported by > Poger and co-workers (see http://pubs.acs.org/doi/abs/ > 10.1021/acs.jctc.7b00178?src=recsys). This is the fastest setup that will > give you the 'correct' membrane properties with the group scheme. > > 2. The combination of reaction field with Verlet and all cutoffs set to > 1.4 does not give the correct membrane properties for DPPC (these are my > own results). Using the group scheme with this setup is fine but slower > than the twin-range setup mentioned above. You should therefore use the > group setup if using reaction-field with this force field. If you wish to > use PME the membrane will be more ordered. However, Verlet and group > schemes give the same results for PME (again my results), > > Regarding the second point, can anyone shed some more light onto why using > the Verlet scheme would result in substantially different membrane > properties to the group scheme with a single 1.4 nm cutoff and > reaction-field (PME gives the same membrane properties using these two > setups)? > > Cheers > > Tom > > From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se [ > gromacs.org_gmx-users-boun...@maillist.sys.kth.se] on behalf of Mark > Abraham [mark.j.abra...@gmail.com] > Sent: 22 September 2017 12:41 > To: gmx-us...@gromacs.org; gromacs.org_gmx-users@maillist.sys.kth.se > Subject: Re: [gmx-users] Gromos54a7 electrostatics interactions ? > > Hi, > > On Fri, Sep 22, 2017 at 10:21 AM Sim gmx wrote: > > > Hi! > > > > I would like to do simulations of lipids bilayers with gromos54a7 > > parameters. To do so, I want to use the same mdp parameters as Poger et > al. > > (the authors). > > > > In their papers, they write : "Nonbonded interactions were evaluated > using > > a twin-range cutoff scheme: interactions falling within the 0.8-nm > > short-range cutoff were calculated every step, whereas interactions > falling > > within the 1.4-nm long-range cutoff were updated every 10 fs, together > with > > the pair list. A reaction-field correction was applied to account for the > > truncation of the electrostatic interactions beyond the long-range cutoff > > using a relative dielectric permittivity constant of 62, as appropriate > for > > SPC water" > > > > Note that such twin-range multiple stepping schemes have only ever been > supported in GROMACS in the group cutoff scheme, and not at all in the most > recent versions. See (older versions of) the reference manual for > discussion of known issues with the twin-range scheme. However, parameters > derived with this irreversible (and thus unphysical) scheme have usually > been shown to be usable outside that scheme, but obviously there's a higher > burden of validation bourne by a the user in that case. > > From this, I conclude that my mdp file should contain something like (among > > other parameters): > > > > dt=0.002 > > vdw-type = cut-off > > rlist = 0.8 > > nstlist = 5 > > rvdw = 1.4 > > coulombtype = reaction-field > > epsilon-rf = 62 > > > > My questions are: >
[gmx-users] Gromos54a7 electrostatics interactions ?
Hi! I would like to do simulations of lipids bilayers with gromos54a7 parameters. To do so, I want to use the same mdp parameters as Poger et al. (the authors). In their papers, they write : "Nonbonded interactions were evaluated using a twin-range cutoff scheme: interactions falling within the 0.8-nm short-range cutoff were calculated every step, whereas interactions falling within the 1.4-nm long-range cutoff were updated every 10 fs, together with the pair list. A reaction-field correction was applied to account for the truncation of the electrostatic interactions beyond the long-range cutoff using a relative dielectric permittivity constant of 62, as appropriate for SPC water" >From this, I conclude that my mdp file should contain something like (among other parameters): dt=0.002 vdw-type = cut-off rlist = 0.8 nstlist = 5 rvdw = 1.4 coulombtype = reaction-field epsilon-rf = 62 My questions are: 1) Does "relative dielectric permittivity constant" indeed mean "epsilon-rf" here (not epsilon-r) ? 2) What about the coulomb cut-off (rcoulomb) ? I think that in gromos53a6, rcoulomb is often set to 0.9 (here I guess it would be 0.8 to match the rlist). However, if the reaction-field correction is applied "to account for the truncation of the electrostatic interactions beyond *the long-range cutoff*", I would set rcoulomb to 1.4. As no explicit reference to rcoulomb is done in the papers, I fear to miss something here. 3) If rcoulomb has indeed to be set to 1.4 as rvdw, it becomes possible to use a verlet cut-off scheme to benefit from GPU acceleration. However, when verlet cut-off scheme is used, mdrun shifts the nstlist and rlist to higher values. Isn't it likely to impact the simulation reliability in such cases ? Thank you in advance for your replies! -- 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.
[gmx-users] K+ ions in gromos53a6 FF ?
Hi, It seems well established that Na+ ions have a condensing effect on Berger lipid bilayers, see for instance https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3000517/ To circumvent this inconvenience, it is advised to use larger cations, such as K+ or TMA. It appears to me that K+ should be easier to use and to justify (I might already be wrong here, feel free to correct me if necessary). However, I just discovered that K+ ions were not present by default in gromos53a6 FF. Could please someone tell me why ? and which non bonded parameters should I add for K+ ions ? I found c6 and c12 values here http://pubs.acs.org/doi/abs/10.1021/ct9000763 but I'm not sure if it is totally reliable. Does anyone have other sources ? Thank you in advance ! -- 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.
Re: [gmx-users] Manual refinement of ATB topologies ?
Hi there, Thanks for the reply ! (and sorry for the delay...) 2016-12-23 19:25 GMT+01:00 Justin Lemkul : > > > On 12/23/16 3:20 AM, Sim gmx wrote: > >> 2016-12-22 14:40 GMT+01:00 Justin Lemkul : >> >> >>> >>> On 12/22/16 8:25 AM, Sim gmx wrote: >>> >>> Hello, >>>> >>>> 2016-12-22 13:56 GMT+01:00 Justin Lemkul : >>>> >>>> >>>> >>>>> On 12/22/16 4:28 AM, Sim gmx wrote: >>>>> >>>>> Hello, >>>>> >>>>>> >>>>>> Thank you very much for your help! >>>>>> Good reference indeed! Just to be sure: >>>>>> - ATB gave me HC and C atom types instead of 'CR1' for the CH groups >>>>>> involved in double bonds. Would it be right to merge the two atomtypes >>>>>> (i.e. deleting the HC atoms and changing C atoms to CR1) and add up >>>>>> their >>>>>> respective charges to get the charge of each CR1 atoms ? >>>>>> >>>>>> >>>>>> Why do this? Few GROMOS species even use CR1 any more, as it appears >>>>> to >>>>> be a backwards compatibility with old GROMOS parameter sets that used a >>>>> UA >>>>> aromatic type. Phe, Tyr, etc. use C-HC as these are somewhat "polar" >>>>> C-H >>>>> bonds so the H is represented explicitly. I'd leave the parameters >>>>> alone, >>>>> mostly because you need the H and associated parameters there to >>>>> determine >>>>> the geometry of the double bond. >>>>> >>>>> >>>>> Because in the itp files from the suggested paper above (Poger et al.) >>>> they >>>> used CR1 atomtypes for the CH groups involved in double bonds. I would >>>> be >>>> a >>>> bit afraid if I had to justify in a reviewing process why I took their >>>> parameters for the double bond but did not use the same atom typing, I >>>> might be a bit paranoid though. >>>> >>>> >>> I just remain skeptical that such a representation is physically valid. >>> Just representing a double bond as an uncharged entity in the middle of >>> an >>> uncharged chain, while consistent with the force field's underlying >>> theory, >>> seems quite inadequate to me. If ATB is suggesting an alternate, it >>> should >>> be explored. I think this is polar character that is not accounted for >>> in >>> the simplistic uncharged model. To what extent that affects the dynamics >>> needs to be examined. >>> >>> >> I see your point. Indeed it looks a bit strange, especially when comparing >> with aromatic structures from amino acids. However, such uncharged double >> bonds are also seen in the widely used lipid parameters from Peter >> Tieleman >> for Berger Lipids (even though the forcefields are different, I guess this >> comparison is acceptable). It does not mean that it is perfect, but >> hopefully that it is usable. >> >> >> >>> If I define an improper dihedral with a torsion angle of 180°, wouldn't >>> it >>> >>>> be a trans double bond anyway (no matter the presence or absence of the >>>> H >>>> atoms) ? >>>> >>>> >>> Impropers keep planar groups planar; they do not keep bonds in cis or >>> trans orientation. >>> >>> >> OK. But then I don't get the point of creating a gi_4 in gromos54a7 that >> is: >> #define gi_4 180.0 167.42309 >> ; planar groups 40 >> >> while there is already a gi_1 that is >> >> #define gi_1 0.0 167.42309 >> ; planar groups 40 >> >> Am I wrong if I write that the only difference is the ideal angle that >> shifts from 0 to 180° ? >> The use of gi_1 or gi_4 is the only difference I've noticed from the itp >> files of Poger et al. cited above between their trans and cis double >> bonds. >> >> > The convention of impropers depends on how the atom order is given. Both > are saying "keep the central atom planar" but perhaps the other atoms are > listed in a different order. > > I don't get this one. In the paper, they parametrized two lipids with the same sequence CH - CI = CJ - CK, but for one the double bond is cis, and for the other one it's a trans double bond. F
Re: [gmx-users] Manual refinement of ATB topologies ?
2016-12-22 14:40 GMT+01:00 Justin Lemkul : > > > On 12/22/16 8:25 AM, Sim gmx wrote: > >> Hello, >> >> 2016-12-22 13:56 GMT+01:00 Justin Lemkul : >> >> >>> >>> On 12/22/16 4:28 AM, Sim gmx wrote: >>> >>> Hello, >>>> >>>> Thank you very much for your help! >>>> Good reference indeed! Just to be sure: >>>> - ATB gave me HC and C atom types instead of 'CR1' for the CH groups >>>> involved in double bonds. Would it be right to merge the two atomtypes >>>> (i.e. deleting the HC atoms and changing C atoms to CR1) and add up >>>> their >>>> respective charges to get the charge of each CR1 atoms ? >>>> >>>> >>> Why do this? Few GROMOS species even use CR1 any more, as it appears to >>> be a backwards compatibility with old GROMOS parameter sets that used a >>> UA >>> aromatic type. Phe, Tyr, etc. use C-HC as these are somewhat "polar" C-H >>> bonds so the H is represented explicitly. I'd leave the parameters >>> alone, >>> mostly because you need the H and associated parameters there to >>> determine >>> the geometry of the double bond. >>> >>> >> Because in the itp files from the suggested paper above (Poger et al.) >> they >> used CR1 atomtypes for the CH groups involved in double bonds. I would be >> a >> bit afraid if I had to justify in a reviewing process why I took their >> parameters for the double bond but did not use the same atom typing, I >> might be a bit paranoid though. >> > > I just remain skeptical that such a representation is physically valid. > Just representing a double bond as an uncharged entity in the middle of an > uncharged chain, while consistent with the force field's underlying theory, > seems quite inadequate to me. If ATB is suggesting an alternate, it should > be explored. I think this is polar character that is not accounted for in > the simplistic uncharged model. To what extent that affects the dynamics > needs to be examined. > I see your point. Indeed it looks a bit strange, especially when comparing with aromatic structures from amino acids. However, such uncharged double bonds are also seen in the widely used lipid parameters from Peter Tieleman for Berger Lipids (even though the forcefields are different, I guess this comparison is acceptable). It does not mean that it is perfect, but hopefully that it is usable. > > If I define an improper dihedral with a torsion angle of 180°, wouldn't it >> be a trans double bond anyway (no matter the presence or absence of the H >> atoms) ? >> > > Impropers keep planar groups planar; they do not keep bonds in cis or > trans orientation. > OK. But then I don't get the point of creating a gi_4 in gromos54a7 that is: #define gi_4 180.0 167.42309 ; planar groups 40 while there is already a gi_1 that is #define gi_1 0.0 167.42309 ; planar groups 40 Am I wrong if I write that the only difference is the ideal angle that shifts from 0 to 180° ? The use of gi_1 or gi_4 is the only difference I've noticed from the itp files of Poger et al. cited above between their trans and cis double bonds. > > Do you think I should leave the HC atoms alone and include 2 improper >> dihedrals for each double bond ? One for H-C=C-C and the other one for >> C-C=C-H (both with a torsion angle of 0, resulting in a trans double >> bond) ? >> >> > If it's me doing it, I'd test both topologies. I've done simulations > with, POPC and a simple, uncharged model and didn't notice anything out of > the ordinary but I've grown skeptical. You have multiple double bonds in > your compound, separated by only one bond, and their properties may depend > on a more precise electrostatic representation. > > -Justin > > To be sure that we are talking about the same thing, "both topologies" means the double bond parameters as they exactly come from ATB server *and* the double bond parameters modified according to Poger et al., right ? How would you do then to select the "best one" ? Except if they exhibit totally different behavior (which is unlikely, I guess), it seems quite complicated to establish. Still I will give it a try! It is true that this proximity between the two double bonds could have a marked effect on electrostatics. Thanks again for your reply. -- 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.
Re: [gmx-users] Manual refinement of ATB topologies ?
Hello, 2016-12-22 13:56 GMT+01:00 Justin Lemkul : > > > On 12/22/16 4:28 AM, Sim gmx wrote: > >> Hello, >> >> Thank you very much for your help! >> Good reference indeed! Just to be sure: >> - ATB gave me HC and C atom types instead of 'CR1' for the CH groups >> involved in double bonds. Would it be right to merge the two atomtypes >> (i.e. deleting the HC atoms and changing C atoms to CR1) and add up their >> respective charges to get the charge of each CR1 atoms ? >> > > Why do this? Few GROMOS species even use CR1 any more, as it appears to > be a backwards compatibility with old GROMOS parameter sets that used a UA > aromatic type. Phe, Tyr, etc. use C-HC as these are somewhat "polar" C-H > bonds so the H is represented explicitly. I'd leave the parameters alone, > mostly because you need the H and associated parameters there to determine > the geometry of the double bond. > Because in the itp files from the suggested paper above (Poger et al.) they used CR1 atomtypes for the CH groups involved in double bonds. I would be a bit afraid if I had to justify in a reviewing process why I took their parameters for the double bond but did not use the same atom typing, I might be a bit paranoid though. If I define an improper dihedral with a torsion angle of 180°, wouldn't it be a trans double bond anyway (no matter the presence or absence of the H atoms) ? Do you think I should leave the HC atoms alone and include 2 improper dihedrals for each double bond ? One for H-C=C-C and the other one for C-C=C-H (both with a torsion angle of 0, resulting in a trans double bond) ? > > - gromos53a6, the FF that I use, does not include gi_4 parameter that seems >> to be gi_1 with a 180° angle value instead of 0 (for the trans double >> bond). I guess I can just add this line in my 53a6 ffbonded.itp file or >> manually include the right parameters in the topology file of my molecule. >> Basically, there is no need to switch to the whole 54a7 FF in my case ? >> >> > Right. > > -Justin > > Thanks for your reply ! > > Have a nice day ! >> >> 2016-12-21 15:27 GMT+01:00 Piggot T. : >> >> Hi, >>> >>> This paper, and in particular the SI which has parameters for a lipid >>> tail >>> with a conjugated double bond, may be of interest here: >>> >>> http://pubs.acs.org/doi/pdf/10.1021/acs.jpcb.5b00958 >>> >>> From a very quick look at the work, they have used the standard double >>> bond parameters (itps are given in the SI) and claim it works ok (e.g. >>> though similarities in order parameters to other works). Given these are >>> the original developers of the GROMOS54A7 lipids, I would suggest that >>> this >>> is therefore probably a reasonable thing to also do for this bit of your >>> molecule. >>> >>> Cheers >>> >>> Tom >>> >>> >>> From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se [ >>> gromacs.org_gmx-users-boun...@maillist.sys.kth.se] on behalf of Sim gmx >>> [ >>> sim...@gmail.com] >>> Sent: 21 December 2016 09:49 >>> To: gmx-us...@gromacs.org >>> Subject: Re: [gmx-users] Manual refinement of ATB topologies ? >>> >>> Thank you for your reply. >>> >>> I will try this and, at the same time, try to get started with CHARMM36. >>> >>> About the bonded parameters, I guess I have to keep for instance the ATB >>> parameters for the peculiar cyclic structure, but what about let's say >>> the >>> two double bonds ? I found the 53a6 topology of POPC from lipidbook, >>> which >>> includes a double bond. The bond and angle types should be the same, but >>> I >>> would expect a difference for dihedrals since in my case there are two >>> double bonds in a row. >>> >>> Yes, to the CGenFF website. OK, I will not care too much so. >>> >>> 2016-12-21 3:16 GMT+01:00 Justin Lemkul : >>> >>> >>>> >>>> On 12/19/16 9:43 AM, Sim gmx wrote: >>>> >>>> Again, thanks a lot for taking the time to reply me. >>>>> >>>>> So you think I should submit this model compound to ATB as a "starting >>>>> block" for my molecule ? >>>>> Actually my whole molecule looks like this: >>>>> >>>>> (ring system)-(C=O)-CH=CH-CH=CH-CH2-CH2-CH2-CH2-CH3 >>>>> >>>>> So there is this annoying second double bond that (I guess
Re: [gmx-users] Manual refinement of ATB topologies ?
Hello,
Thank you very much for your help!
Good reference indeed! Just to be sure:
- ATB gave me HC and C atom types instead of 'CR1' for the CH groups
involved in double bonds. Would it be right to merge the two atomtypes
(i.e. deleting the HC atoms and changing C atoms to CR1) and add up their
respective charges to get the charge of each CR1 atoms ?
- gromos53a6, the FF that I use, does not include gi_4 parameter that seems
to be gi_1 with a 180° angle value instead of 0 (for the trans double
bond). I guess I can just add this line in my 53a6 ffbonded.itp file or
manually include the right parameters in the topology file of my molecule.
Basically, there is no need to switch to the whole 54a7 FF in my case ?
Have a nice day !
2016-12-21 15:27 GMT+01:00 Piggot T. :
> Hi,
>
> This paper, and in particular the SI which has parameters for a lipid tail
> with a conjugated double bond, may be of interest here:
>
> http://pubs.acs.org/doi/pdf/10.1021/acs.jpcb.5b00958
>
> From a very quick look at the work, they have used the standard double
> bond parameters (itps are given in the SI) and claim it works ok (e.g.
> though similarities in order parameters to other works). Given these are
> the original developers of the GROMOS54A7 lipids, I would suggest that this
> is therefore probably a reasonable thing to also do for this bit of your
> molecule.
>
> Cheers
>
> Tom
>
>
> From: gromacs.org_gmx-users-boun...@maillist.sys.kth.se [
> gromacs.org_gmx-users-boun...@maillist.sys.kth.se] on behalf of Sim gmx [
> sim...@gmail.com]
> Sent: 21 December 2016 09:49
> To: gmx-us...@gromacs.org
> Subject: Re: [gmx-users] Manual refinement of ATB topologies ?
>
> Thank you for your reply.
>
> I will try this and, at the same time, try to get started with CHARMM36.
>
> About the bonded parameters, I guess I have to keep for instance the ATB
> parameters for the peculiar cyclic structure, but what about let's say the
> two double bonds ? I found the 53a6 topology of POPC from lipidbook, which
> includes a double bond. The bond and angle types should be the same, but I
> would expect a difference for dihedrals since in my case there are two
> double bonds in a row.
>
> Yes, to the CGenFF website. OK, I will not care too much so.
>
> 2016-12-21 3:16 GMT+01:00 Justin Lemkul :
>
> >
> >
> > On 12/19/16 9:43 AM, Sim gmx wrote:
> >
> >> Again, thanks a lot for taking the time to reply me.
> >>
> >> So you think I should submit this model compound to ATB as a "starting
> >> block" for my molecule ?
> >> Actually my whole molecule looks like this:
> >>
> >> (ring system)-(C=O)-CH=CH-CH=CH-CH2-CH2-CH2-CH2-CH3
> >>
> >> So there is this annoying second double bond that (I guess) I am obliged
> >> to
> >> include into the model I would submit to ATB. Thus I have the feeling
> that
> >> the shortest molecule that I could use as a model compound would be:
> >>
> >> (ring system)-(C=O)-CH=CH-CH=CH-CH3
> >>
> >> which is my whole molecule minus butane. So, couldn't I use the
> >> ATB-topology of my whole molecule (that I already have) and change these
> >> last methyl groups that should not carry any charge ?
> >>
> >> I would do two things:
> >
> > (ring system)-(C=O)-CH3
> >
> > and then
> >
> > (ring system)-(C=O)-CH=CH-CH=CH-CH2-CH3
> >
> > This will tell you how you might have to reapportion some of the charges,
> > as the neighboring CH2 might correctly be assigned some small charge and
> > having it as a terminal atom may not be wise. The terminal CH3 in the
> > model is the (n-3) carbon; each of these last three should have zero
> > charge, so you can adjust the charges as needed if anything is assigned
> > from the model.
> >
> > Nice to read your considerations about Berger and gromos FF, I easily
> hung
> >> up on those things... (if/when you have some time, you can get a
> >> confirmation here
> >> https://mailman-1.sys.kth.se/pipermail/gromacs.org_gmx-users
> >> /2016-December/109831.html
> >> )
> >>
> >>
> >> OK, it sounds great indeed, I should definitely have a look at this FF.
> Is
> >> it possible to quickly get started with CHARMM ? Possible to launch the
> >> first simulations in one week or so ? Also, I get a warning message when
> >> trying to connect to CGenFF ("unsafe connexion"), should I ignore this ?
> >>
> >>
> > To the CGenFF website? There should be no security issues; maybe the
> >
Re: [gmx-users] Manual refinement of ATB topologies ?
Thank you for your reply.
I will try this and, at the same time, try to get started with CHARMM36.
About the bonded parameters, I guess I have to keep for instance the ATB
parameters for the peculiar cyclic structure, but what about let's say the
two double bonds ? I found the 53a6 topology of POPC from lipidbook, which
includes a double bond. The bond and angle types should be the same, but I
would expect a difference for dihedrals since in my case there are two
double bonds in a row.
Yes, to the CGenFF website. OK, I will not care too much so.
2016-12-21 3:16 GMT+01:00 Justin Lemkul :
>
>
> On 12/19/16 9:43 AM, Sim gmx wrote:
>
>> Again, thanks a lot for taking the time to reply me.
>>
>> So you think I should submit this model compound to ATB as a "starting
>> block" for my molecule ?
>> Actually my whole molecule looks like this:
>>
>> (ring system)-(C=O)-CH=CH-CH=CH-CH2-CH2-CH2-CH2-CH3
>>
>> So there is this annoying second double bond that (I guess) I am obliged
>> to
>> include into the model I would submit to ATB. Thus I have the feeling that
>> the shortest molecule that I could use as a model compound would be:
>>
>> (ring system)-(C=O)-CH=CH-CH=CH-CH3
>>
>> which is my whole molecule minus butane. So, couldn't I use the
>> ATB-topology of my whole molecule (that I already have) and change these
>> last methyl groups that should not carry any charge ?
>>
>> I would do two things:
>
> (ring system)-(C=O)-CH3
>
> and then
>
> (ring system)-(C=O)-CH=CH-CH=CH-CH2-CH3
>
> This will tell you how you might have to reapportion some of the charges,
> as the neighboring CH2 might correctly be assigned some small charge and
> having it as a terminal atom may not be wise. The terminal CH3 in the
> model is the (n-3) carbon; each of these last three should have zero
> charge, so you can adjust the charges as needed if anything is assigned
> from the model.
>
> Nice to read your considerations about Berger and gromos FF, I easily hung
>> up on those things... (if/when you have some time, you can get a
>> confirmation here
>> https://mailman-1.sys.kth.se/pipermail/gromacs.org_gmx-users
>> /2016-December/109831.html
>> )
>>
>>
>> OK, it sounds great indeed, I should definitely have a look at this FF. Is
>> it possible to quickly get started with CHARMM ? Possible to launch the
>> first simulations in one week or so ? Also, I get a warning message when
>> trying to connect to CGenFF ("unsafe connexion"), should I ignore this ?
>>
>>
> To the CGenFF website? There should be no security issues; maybe the
> certificate is out of date.
>
> -Justin
>
>
> Thank you, have a nice day !
>>
>> 2016-12-19 14:13 GMT+01:00 Justin Lemkul :
>>
>>
>>>
>>> On 12/19/16 7:50 AM, Sim gmx wrote:
>>>
>>> Thank you for your answer.
>>>>
>>>> "Unfortunately", this molecule has a peculiar structure with a 5-atoms
>>>> cycle (including a nitrogen atom) directly bound to a C=O itself bound
>>>> to
>>>> a
>>>> CH involved in a double bound. I guess that this nearness between the
>>>> groups should lead to some "hardly predictable" charge distribution
>>>> within
>>>> the molecule. Hence, if I submit for instance only the 5-atoms cyclic
>>>> part
>>>> to ATB and take the C=O parameters from an existing topology, I guess I
>>>> will have a hard time to merge the two parts, am I wrong ?
>>>>
>>>> If I don't get you wrong, my 'instinctive behavior' shares some
>>>> similarities with what you suggest (replacing, wherever it is possible,
>>>> ATB
>>>> parameters by 'known parameters'). But if I don't submit the whole
>>>> molecule to ATB, then I don't know how to get "reliable" atomic charges
>>>> ?
>>>>
>>>>
>>>> This is common to all additive force fields. You need a suitable model
>>> compound, one that includes linker portions that can be merged with
>>> neighboring functional groups by combining charges and applying/modifying
>>> known dihedrals. What I would do is try to parametrize:
>>>
>>> (ring system)-C=O-CH=CH-CH3
>>>
>>> and whatever might be a suitable flanking group for the ring (e.g. methyl
>>> or ethyl, etc) if it is in the middle of the acyl chain. There may be
>>> partial charges on those neighboring methyl/methylene groups. That would
>>> be
Re: [gmx-users] How to use Höltje's cholesterol parameters ?
Hello, Thank you very much for your reply. You are probably right. This is quite frustrating to observe that everyone sometimes seems to use its own recipe for MD simulations of bilayers without giving enough details to allow others to compare or exactly reproduce their results. In this regard, I must say that your paper comparing several forcefields for their ability to reproduce phosphatidylcholine bilayers was a remarkably useful contribution imo. I could indeed test these things by myself and, in a way, I started to do so since I've launched 200 ns equilibrations of bilayers built with solution 1 and 2. Unfortunately, it becomes complicated because I don't have experimental data on which I can rely to select the best solution. Moreover, I slightly modified the topology to get sitosterol instead of cholesterol (just a minor methyl change from cholesterol) to get a biologically relevant system for my work, making even less likely to find experimental data for this. Both solutions result in a consistent ordering effect when compared with pure phosphatidylcholine bilayers, but this ordering effect is slightly different when comparing the solutions with each other. Solution 1 also seems to lead to a slightly higher area per lipid than solution 2, but here again, which one is closer from the "truth" ? I will for sure have a look at the discussion you mention. I am indeed simulating PC phosopholipids, so I think it shoudl be OK to use Berger Lipids to this purpose. I think I will at least try to simulate something with the 54A7 parameters of Poger et al. since it does not require a lot of work from where I am at this point and since it would already make a comparison possible. About CHARMM36 (or other forcefield), I will for sure give it a try for my next project, but I am not sure if it will be worth doing here as I have already lost some time in refining simulation parameters and given the poor results that I got so far... Thank you again for your nice reply. 2016-12-20 15:44 GMT+01:00 Thomas Piggot : > Hi, > > Not sure how much I can help here as I've not used these Holtje parameters > or indeed even simulated cholesterol all that much before but hopefully I > say a couple of general things that might be of use. > > Firstly, this is a good question and I think that lack of responses is > probably due to the fact the no-one has really tested these different types > of combinations. If someone knows otherwise, please feel free to correct > me. You could obviously test these things yourself, but that would require > a fair amount of work. What I do know about the Berger/Holtje combination > is that it is thought to result in a too much of an ordering (see, for > example, some of the discussions at http://nmrlipids.blogspot.co.u > k/2016/07/nmrlipids-iii-preliminary-observations.html). I'm unsure if > this is with the standard cholesterol tail atomtypes or with Berger types, > as you suggest you might want to use. > > A second point is related to the Berger force field in general. Unless you > are simulating PC phospholipids, you should avoid using this force field. > There are several papers that show that things don't work well for > different non-PC based lipids. > > Finally, and you sort of touched upon this, to avoid these issues you > could just use a different force field. You mention that you already have > GROMOS topologies for your small molecules and that there are cholesterol > parameters available from the ATB; there are also compatible phospholipid > parameters too. For PC lipids you have the choice of the 53A6L/54A7 > parameters of Poger et al. (included in the 54A7 rtp and also available > from the ATB), or the Kukol/GROMOS-CKP parameters (these ones are available > to download from Lipidbook or I can send stuff off list). For these latter > parameters, there are also lots of different lipids types available which > work pretty well in general (like any force field, I definitely wouldn't > claim that they are perfect though). You could also switch to a completely > different force field all together and use, for example, one of the > all-atom CHARMM36, Slipids or LIPID14 force fields. These will likely have > the lipid parameters you need but you would need to parameterise the small > molecules. The latter two are AMBER based and so you could use GAFF for > this, for CHARMM36 you can use CGenFF. Frankly, I'd suggest doing the > simulations using a couple of different force fields anyway to try and be > sure of anything you see, if you have the time/compute to do so. > > Hopefully that is some sort of help, sorry I can't give more specific > advice directly on your questions. > > Cheers > > Tom > > > On 20/12/16 14:09, Sim gmx wrote: > >> Anyone ? >> Do you think it does not
Re: [gmx-users] How to use Höltje's cholesterol parameters ?
Anyone ? Do you think it does not deserve any attention given the similiraties between GROMOS87 and GROMOS96 FF ? 2016-12-12 9:38 GMT+01:00 Sim gmx : > Please, could someone help me with that ? Are my questions unclear ? > > 2016-12-09 9:48 GMT+01:00 Sim gmx : > >> Hello everyone, >> >> I am currently working on interactions between small biomolecules and >> bilayers. Phospholipids parameters come from Peter Tieleman's website >> (Berger lipids forcefield) and the small compounds are parametrized for >> gromos53a6. I would like to add cholesterol to my bilayers, which is very >> frequently done with Höltje cholesterol parameters (see e.g. >> http://pubs.acs.org/doi/full/10.1021/ja211929h ). However, these Höltje >> parameters were originally designed for the ffgmx forcefield, which is >> quite old. >> >> The way we should include these parameters in a Berger lipids - >> gromos53a6 mixed forcefield has already raised some questions on the >> mailing list: http://comments.gmane.org/gman >> e.science.biology.gromacs.user/68478 >> >> However, it remains unclear to me. I guess we can use the bonded >> parameters as they are written in the original topology from Höltje, but it >> becomes more complicated when talking about the non bonded interactions. >> Every atomtypes but two (CB and CR61) from ffgmx also exist in gromos53a6 >> (and are thus included in the gromos53a6 forcefield). Hence, I think there >> are 3 possible ways to make a simulation run without crashing when >> including this cholesterol to a berger lipid - gromos53a6 forcefield: >> >> 1) Keeping the cholesterol topology file unchanged, and adding the >> atomtypes 'CB' and 'CR61' to the forcefield file 'ffnonbonded.itp', with >> their parameters coming from the ffgmx forcefield. It means that each >> cholesterol will be seen as a "hybrid object", with most of the atomtypes >> being gromos53a6 ones, and CB and CR61 being ffgmx atomtypes. Non bonded >> interaction involving CB or CR61 atomtypes will be computed with the >> standard combination rule. >> >> 2) Keeping the Berger lipid - gromos53a6 forcefield unchanged, and >> changing the atomtype 'CB' to 'C' and the atomtype 'CR61' to 'CR1' into the >> cholesterol topology file, C and CR1 being the corresponding atomtypes >> found in gromos53a6. It means that each cholesterol will be seen as a >> "gromos53a6" object for the non bonded interactions. >> >> 3) Changing every atomtype from the cholesterol topology file to make >> them different from gromos53a6 atomtypes (for instance: CH2 becomes CH2F >> (for ffgmx)) and adding all these ffgmx specific atomtypes in the >> forcefield file 'ffnonbonded.itp' with the proper parameters. It means that >> each cholesterol will be seen as a "ffgmx object", each non bonded >> interaction being computed with the standard combination rule. >> >> Solution 1 seems to be quite obvious, but it sounds a bit weird to me, >> because it mixes up ffgmx and 53a6 interactions. Solution 2 seems more >> consistent, but if we use "pure" gromos53a6 non bonded interactions, maybe >> we should also "translate" bonded parameters from ffgmx to gromos53a6 ? >> Solution 3 is maybe the most logical solution, but it seems that ffgmx is >> now considered to be deprecated... >> >> The question becomes even more complicated when considering the fact that >> CH2 and CH3 atomtypes could lead to overcondensed bilayers, according to >> some authors who advise to switch them to 'LP2' and 'LP3' Berger lipid >> atomtypes. >> >> It is possible that those solutions give quite similar results (if ffgmx >> and gromos53a6 forcefields are "similar enough"), but I am very curious to >> know the 'usual' protocol that is followed when people only write "Höltje >> parameters were used". >> >> Another solution would be to use the cholesterol topology file found on >> ATB (manual validation), frequently used by Pr. Alan E. Mark, but never >> used with Berger lipids phospholipids... >> >> Thank you in advance for your help! >> > > -- 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.
Re: [gmx-users] Manual refinement of ATB topologies ?
Again, thanks a lot for taking the time to reply me.
So you think I should submit this model compound to ATB as a "starting
block" for my molecule ?
Actually my whole molecule looks like this:
(ring system)-(C=O)-CH=CH-CH=CH-CH2-CH2-CH2-CH2-CH3
So there is this annoying second double bond that (I guess) I am obliged to
include into the model I would submit to ATB. Thus I have the feeling that
the shortest molecule that I could use as a model compound would be:
(ring system)-(C=O)-CH=CH-CH=CH-CH3
which is my whole molecule minus butane. So, couldn't I use the
ATB-topology of my whole molecule (that I already have) and change these
last methyl groups that should not carry any charge ?
Nice to read your considerations about Berger and gromos FF, I easily hung
up on those things... (if/when you have some time, you can get a
confirmation here
https://mailman-1.sys.kth.se/pipermail/gromacs.org_gmx-users/2016-December/109831.html
)
OK, it sounds great indeed, I should definitely have a look at this FF. Is
it possible to quickly get started with CHARMM ? Possible to launch the
first simulations in one week or so ? Also, I get a warning message when
trying to connect to CGenFF ("unsafe connexion"), should I ignore this ?
Thank you, have a nice day !
2016-12-19 14:13 GMT+01:00 Justin Lemkul :
>
>
> On 12/19/16 7:50 AM, Sim gmx wrote:
>
>> Thank you for your answer.
>>
>> "Unfortunately", this molecule has a peculiar structure with a 5-atoms
>> cycle (including a nitrogen atom) directly bound to a C=O itself bound to
>> a
>> CH involved in a double bound. I guess that this nearness between the
>> groups should lead to some "hardly predictable" charge distribution within
>> the molecule. Hence, if I submit for instance only the 5-atoms cyclic part
>> to ATB and take the C=O parameters from an existing topology, I guess I
>> will have a hard time to merge the two parts, am I wrong ?
>>
>> If I don't get you wrong, my 'instinctive behavior' shares some
>> similarities with what you suggest (replacing, wherever it is possible,
>> ATB
>> parameters by 'known parameters'). But if I don't submit the whole
>> molecule to ATB, then I don't know how to get "reliable" atomic charges ?
>>
>>
> This is common to all additive force fields. You need a suitable model
> compound, one that includes linker portions that can be merged with
> neighboring functional groups by combining charges and applying/modifying
> known dihedrals. What I would do is try to parametrize:
>
> (ring system)-C=O-CH=CH-CH3
>
> and whatever might be a suitable flanking group for the ring (e.g. methyl
> or ethyl, etc) if it is in the middle of the acyl chain. There may be
> partial charges on those neighboring methyl/methylene groups. That would
> be normal. But putting partial charges on UA carbon atoms multiple bonds
> away is not intuitive, given the philosophy of the force field. I would
> assume positive-positive repulsion would perturb the bilayer, unless the LJ
> mask the issue.
>
> You underline another important thing to consider: the choice of the right
>> forcefield. Until now I've been working with berger lipids as forcefield
>> for my bilayers (initially following one of your tutorials, by the way
>> thanks a lot for this very helpful work !) in combination with small
>> gromos53a6 molecules. Here, since my molecule includes a large acyl chain,
>> it could be non ideal to use gromos53a6 parameters while the lipids with
>> which it should interact are parametrized with berger lipids. Maybe berger
>> - berger non-bonded interactions would be better for these mainly
>> hydrophobic interactions ? Nevertheless I don't see how I could create a
>> berger topology for such a peculiar molecule, especially because I don't
>> know any ATB-like for this FF.
>>
>
> Berger lipids were derived from old GROMOS parameters and some aspects of
> OPLS, so don't get too hung up on whether or not interactions are
> Berger-Berger or Berger-GROMOS. They're compatible.
>
> Maybe another force field could be used for both the bilayer and my
>> molecule (with the help of a reliable ATB-like website) ? Or would it be
>> better to use gromos53a6 lipids instead of berger lipids ?
>>
>>
> I do everything with the CHARMM force field nowadays. Parametrization is
> straightforward and the CGenFF server parametrizes small molecules and
> model compounds easily, and they can then be converted to GROMACS format
> with a script from the MacKerell group website. The parametrization theory
> and protocol for CHARM
Re: [gmx-users] Manual refinement of ATB topologies ?
Thank you for your answer. "Unfortunately", this molecule has a peculiar structure with a 5-atoms cycle (including a nitrogen atom) directly bound to a C=O itself bound to a CH involved in a double bound. I guess that this nearness between the groups should lead to some "hardly predictable" charge distribution within the molecule. Hence, if I submit for instance only the 5-atoms cyclic part to ATB and take the C=O parameters from an existing topology, I guess I will have a hard time to merge the two parts, am I wrong ? If I don't get you wrong, my 'instinctive behavior' shares some similarities with what you suggest (replacing, wherever it is possible, ATB parameters by 'known parameters'). But if I don't submit the whole molecule to ATB, then I don't know how to get "reliable" atomic charges ? You underline another important thing to consider: the choice of the right forcefield. Until now I've been working with berger lipids as forcefield for my bilayers (initially following one of your tutorials, by the way thanks a lot for this very helpful work !) in combination with small gromos53a6 molecules. Here, since my molecule includes a large acyl chain, it could be non ideal to use gromos53a6 parameters while the lipids with which it should interact are parametrized with berger lipids. Maybe berger - berger non-bonded interactions would be better for these mainly hydrophobic interactions ? Nevertheless I don't see how I could create a berger topology for such a peculiar molecule, especially because I don't know any ATB-like for this FF. Maybe another force field could be used for both the bilayer and my molecule (with the help of a reliable ATB-like website) ? Or would it be better to use gromos53a6 lipids instead of berger lipids ? Thank you in advance ! 2016-12-16 22:58 GMT+01:00 Justin Lemkul : > > > On 12/16/16 7:46 AM, Sim gmx wrote: > >> Hi all, >> >> I would like to know what you consider to be the ideal refinement for a >> topology created by ATB ? >> How far should we go in the manual refinement ? >> >> For instance, ATB gave me a topology for a molecule with an unsaturated >> acyl chain. Here are some potential issues with this topology: >> >> 1) Three methyl groups at the end of the acyl chain (that are "3 methyl >> groups away" from a double bond) carry a small charge (with a net group >> charge of 0, however) >> 2) For the double bonds, parameters are "new parameters" (not found in >> ffbonded.itp file) >> 3) Some bonded parameters in the ATB topology do exist in ffbonded.itp >> file >> but are not supposed to be applied for this kind of bond (example: O - S >> bond parameters are written for a C (involved in a double bond) - CH2 >> bond) >> >> My "instinctive" behavior would be to: >> >> 1) Put a 0 charge to these methyl groups since they should not be charged >> imo >> 2) Look for another gromos53a6 topology that includes a double bond (like >> this one https://lipidbook.bioch.ox.ac.uk/package/show/id/16.html) and >> take >> the double bond parameters from it >> 3) Replace those bonds by correct "default parameters" found in >> ffbonded.itp file, in this case by a "C, CHn - C, CHn" bonded parameter. >> >> However, I don't wish to break an "equilibrium" that ATB could have built >> with some apparently weird parameters. >> >> Hence, is it better to take the ATB topology as it comes, or to try to >> refine it ? If the latter, how far should we go ? Isn't it risky or >> complicated to justify (in a reviewing process, for example :)) ? >> >> > You shouldn't be trying to parametrize an entire lipid all at once, > anyway. You should only be addressing moieties for which parameters do not > exist, and the combining them with known moieties. GROMOS96 has fairly > comprehensive lipid parameters that can be used (though other force fields > may be better, and lipids are quite hard to get right). > > -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
[gmx-users] Manual refinement of ATB topologies ?
Hi all, I would like to know what you consider to be the ideal refinement for a topology created by ATB ? How far should we go in the manual refinement ? For instance, ATB gave me a topology for a molecule with an unsaturated acyl chain. Here are some potential issues with this topology: 1) Three methyl groups at the end of the acyl chain (that are "3 methyl groups away" from a double bond) carry a small charge (with a net group charge of 0, however) 2) For the double bonds, parameters are "new parameters" (not found in ffbonded.itp file) 3) Some bonded parameters in the ATB topology do exist in ffbonded.itp file but are not supposed to be applied for this kind of bond (example: O - S bond parameters are written for a C (involved in a double bond) - CH2 bond) My "instinctive" behavior would be to: 1) Put a 0 charge to these methyl groups since they should not be charged imo 2) Look for another gromos53a6 topology that includes a double bond (like this one https://lipidbook.bioch.ox.ac.uk/package/show/id/16.html) and take the double bond parameters from it 3) Replace those bonds by correct "default parameters" found in ffbonded.itp file, in this case by a "C, CHn - C, CHn" bonded parameter. However, I don't wish to break an "equilibrium" that ATB could have built with some apparently weird parameters. Hence, is it better to take the ATB topology as it comes, or to try to refine it ? If the latter, how far should we go ? Isn't it risky or complicated to justify (in a reviewing process, for example :)) ? Thank you ! -- 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.
Re: [gmx-users] How to use Höltje's cholesterol parameters ?
Please, could someone help me with that ? Are my questions unclear ? 2016-12-09 9:48 GMT+01:00 Sim gmx : > Hello everyone, > > I am currently working on interactions between small biomolecules and > bilayers. Phospholipids parameters come from Peter Tieleman's website > (Berger lipids forcefield) and the small compounds are parametrized for > gromos53a6. I would like to add cholesterol to my bilayers, which is very > frequently done with Höltje cholesterol parameters (see e.g. > http://pubs.acs.org/doi/full/10.1021/ja211929h ). However, these Höltje > parameters were originally designed for the ffgmx forcefield, which is > quite old. > > The way we should include these parameters in a Berger lipids - gromos53a6 > mixed forcefield has already raised some questions on the mailing list: > http://comments.gmane.org/gmane.science.biology.gromacs.user/68478 > > However, it remains unclear to me. I guess we can use the bonded > parameters as they are written in the original topology from Höltje, but it > becomes more complicated when talking about the non bonded interactions. > Every atomtypes but two (CB and CR61) from ffgmx also exist in gromos53a6 > (and are thus included in the gromos53a6 forcefield). Hence, I think there > are 3 possible ways to make a simulation run without crashing when > including this cholesterol to a berger lipid - gromos53a6 forcefield: > > 1) Keeping the cholesterol topology file unchanged, and adding the > atomtypes 'CB' and 'CR61' to the forcefield file 'ffnonbonded.itp', with > their parameters coming from the ffgmx forcefield. It means that each > cholesterol will be seen as a "hybrid object", with most of the atomtypes > being gromos53a6 ones, and CB and CR61 being ffgmx atomtypes. Non bonded > interaction involving CB or CR61 atomtypes will be computed with the > standard combination rule. > > 2) Keeping the Berger lipid - gromos53a6 forcefield unchanged, and > changing the atomtype 'CB' to 'C' and the atomtype 'CR61' to 'CR1' into the > cholesterol topology file, C and CR1 being the corresponding atomtypes > found in gromos53a6. It means that each cholesterol will be seen as a > "gromos53a6" object for the non bonded interactions. > > 3) Changing every atomtype from the cholesterol topology file to make them > different from gromos53a6 atomtypes (for instance: CH2 becomes CH2F (for > ffgmx)) and adding all these ffgmx specific atomtypes in the forcefield > file 'ffnonbonded.itp' with the proper parameters. It means that each > cholesterol will be seen as a "ffgmx object", each non bonded interaction > being computed with the standard combination rule. > > Solution 1 seems to be quite obvious, but it sounds a bit weird to me, > because it mixes up ffgmx and 53a6 interactions. Solution 2 seems more > consistent, but if we use "pure" gromos53a6 non bonded interactions, maybe > we should also "translate" bonded parameters from ffgmx to gromos53a6 ? > Solution 3 is maybe the most logical solution, but it seems that ffgmx is > now considered to be deprecated... > > The question becomes even more complicated when considering the fact that > CH2 and CH3 atomtypes could lead to overcondensed bilayers, according to > some authors who advise to switch them to 'LP2' and 'LP3' Berger lipid > atomtypes. > > It is possible that those solutions give quite similar results (if ffgmx > and gromos53a6 forcefields are "similar enough"), but I am very curious to > know the 'usual' protocol that is followed when people only write "Höltje > parameters were used". > > Another solution would be to use the cholesterol topology file found on > ATB (manual validation), frequently used by Pr. Alan E. Mark, but never > used with Berger lipids phospholipids... > > Thank you in advance for your help! > -- 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.
[gmx-users] How to use Höltje's cholesterol parameters ?
Hello everyone, I am currently working on interactions between small biomolecules and bilayers. Phospholipids parameters come from Peter Tieleman's website (Berger lipids forcefield) and the small compounds are parametrized for gromos53a6. I would like to add cholesterol to my bilayers, which is very frequently done with Höltje cholesterol parameters (see e.g. http://pubs.acs.org/doi/full/10.1021/ja211929h ). However, these Höltje parameters were originally designed for the ffgmx forcefield, which is quite old. The way we should include these parameters in a Berger lipids - gromos53a6 mixed forcefield has already raised some questions on the mailing list: http://comments.gmane.org/gmane.science.biology.gromacs.user/68478 However, it remains unclear to me. I guess we can use the bonded parameters as they are written in the original topology from Höltje, but it becomes more complicated when talking about the non bonded interactions. Every atomtypes but two (CB and CR61) from ffgmx also exist in gromos53a6 (and are thus included in the gromos53a6 forcefield). Hence, I think there are 3 possible ways to make a simulation run without crashing when including this cholesterol to a berger lipid - gromos53a6 forcefield: 1) Keeping the cholesterol topology file unchanged, and adding the atomtypes 'CB' and 'CR61' to the forcefield file 'ffnonbonded.itp', with their parameters coming from the ffgmx forcefield. It means that each cholesterol will be seen as a "hybrid object", with most of the atomtypes being gromos53a6 ones, and CB and CR61 being ffgmx atomtypes. Non bonded interaction involving CB or CR61 atomtypes will be computed with the standard combination rule. 2) Keeping the Berger lipid - gromos53a6 forcefield unchanged, and changing the atomtype 'CB' to 'C' and the atomtype 'CR61' to 'CR1' into the cholesterol topology file, C and CR1 being the corresponding atomtypes found in gromos53a6. It means that each cholesterol will be seen as a "gromos53a6" object for the non bonded interactions. 3) Changing every atomtype from the cholesterol topology file to make them different from gromos53a6 atomtypes (for instance: CH2 becomes CH2F (for ffgmx)) and adding all these ffgmx specific atomtypes in the forcefield file 'ffnonbonded.itp' with the proper parameters. It means that each cholesterol will be seen as a "ffgmx object", each non bonded interaction being computed with the standard combination rule. Solution 1 seems to be quite obvious, but it sounds a bit weird to me, because it mixes up ffgmx and 53a6 interactions. Solution 2 seems more consistent, but if we use "pure" gromos53a6 non bonded interactions, maybe we should also "translate" bonded parameters from ffgmx to gromos53a6 ? Solution 3 is maybe the most logical solution, but it seems that ffgmx is now considered to be deprecated... The question becomes even more complicated when considering the fact that CH2 and CH3 atomtypes could lead to overcondensed bilayers, according to some authors who advise to switch them to 'LP2' and 'LP3' Berger lipid atomtypes. It is possible that those solutions give quite similar results (if ffgmx and gromos53a6 forcefields are "similar enough"), but I am very curious to know the 'usual' protocol that is followed when people only write "Höltje parameters were used". Another solution would be to use the cholesterol topology file found on ATB (manual validation), frequently used by Pr. Alan E. Mark, but never used with Berger lipids phospholipids... Thank you in advance for your help! -- 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.
