Dear Moitrayee,
> I am trying to generate the parameters for a modified amino acid on the red
> server. My job id is P3051. I am using the fragment based approach. I started
> with ACE-XXX-NME, generated the p2n file, checked for chemical
> equivalencing and
> submitted it the red server for mol2 file generation. I also read through
> tutorial
>
> http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php#17
>
> However, I am am getting very confused with the different .mol2 files being
> generated. It would be really helpful if you please suggest how
> should I proceed
> with this.
You decided to generate a C-terminal fragment for your modified amino-acid:
This means you involved two molecules in charge derivation. R.E.D.
will first perform _for information_ charge derivation for each
molecule taken individually (see the directories Mol_m1 & Mol_m2) and
then the "multiple" molecule charge derivation; i.e. the one you are
interested in (See the directory Mol_MM)
if you look this time at the job for a N-terminal fragment:
http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php#16
the approach is highly similar (except that acetate is replaced by
methylammonium and a different INTER-MCC is used).
There is a pdf file that describes all the files generated by R.E.D.
in this N-terminal fragment case: See
http://q4md-forcefieldtools.org/Tutorial/P2N/Nterm-frag-Pept/listing-2mol.pdf
You can easily use this pdf file for the C-terminal fragment, but
simply replacing "N-terminal fragment" by "C-terminal fragment" when
reading this file.
Then once you have understood how the central, N-term and C-term
fragments are generated individually you can apply the automatic
procedure and generate the three fragments with the whole molecule in
a single charge derivation procedure; see:
http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php#24
vs
http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php#25
with the pdf file:
http://q4md-forcefieldtools.org/Tutorial/P2N/All-frag-Pept/listing-6mol.pdf
regards, Francois
>> Dear Moitrayee,
>>
>> This looks like far better. Last comments:
>>
>> - So far the mol3 file format is mainly useful for molecular
>> fragments. You have a whole molecule; thus, the mol2 file format is
>> the best choice (i.e. it can be used as a FF lib in the LEaP program
>> and easily displayed in a graphical program such as vmd where
>> topology, atom names, charges values (& atom types) can be visually
>> checked; and it is directly generated by R.E.D.)...
>>
>> - If you use leaprc.ff99SB (or any newer version) I do not think so
>> you need to build a new frcmod file. All the FF parameters for citrate
>> should be in parm99.dat. Moreover, my feeling is that such an accuracy
>> for bond & angle FF constants in gaff.dat is useless; just compare the
>> values in gaff.dat vs parm99.dat, and read the original papers
>> (parm96, parm98 & parm99).
>>
>> For instance:
>> [fyd.master0 parm]$ egrep "^c3-c3 " gaff.dat
>> c3-c3 303.1 1.5350 SOURCE1 14664 0.0048
>> [fyd.master0 parm]$ egrep "^CT-CT " parm99.dat
>> CT-CT 310.0 1.526 JCC,7,(1986),230; AA, SUGARS
>> -> such an accuracy "303.1" is meaningless: better using parm99.dat...
>> Same remark for:
>> [fyd.master0 parm]$ egrep "^c3-h1 " gaff.dat
>> c3-h1 335.9 1.0930 SOURCE3 2175 0.0082
>> [fyd.master0 parm]$ egrep "^CT-H1 " parm99.dat
>> CT-H1 340.0 1.090 changed from 331 bsd on NMA nmodes; AA, RIBOSE
>> -> such an accuracy "335.9" is meaningless: better using parm99.dat...
>>
>> - The off file format has the same role than the mol3/mol2 file format(s).
>>
>> - I would first try to only constraint the HO-OH-CT-H1 dihedral (in
>> the QM geometry optimization).
>>
>> - At the end, I would only execute:
>> xleap -f leaprc.ff99SB
>> VAR = loadmol2 CIT.mol2
>> saveamberparm VAR VAR.top VAR.crd
>>
>> regards, Francois
>>
>>
>>> Thanks a lot for such a detailed reply and pointers about solving
>>> this problem.
>>> I am new to this method and am being much benefited by your comments and
>>> suggestions.
>>>
>>> I have taken care of all the points that you had mentioned. I have added
>>> hydrogens, I have ensured chemical equivalencing by studying the
>>> p2n file in
>>> pymol, and used two angle constraints. I tried using fewer, but
>>> the resultant
>>> citrate ion was becoming distorted (the CH2 groups were showing
>>> angles similar
>>> in that of sp2, so I used constraints as seen in the structure).
>>>
>>> Then I used the mol3 format for using in leap, I did loadmol3 and
>>> savemol3 in
>>> xleap followed by a saveoff to generate the CIT.off file. I
>>> generate a frcmod
>>> file using parmchk on the mol2 files. I load the files in leap using
>>> loadoff and
>>> saveamberparams command, followed by a saveamberparm to generate
>>> the prmtop and
>>> prmcrd files.
>>>
>>> Please let me know if I am doing it correctly this time. I am
>>> attaching the p2n,
>>> the mol2, the OFF and frcmod files that I am using for the calculation.
>>
>>>> Dear Moitrayee,
>>>>
>>>> Many problems...
>>>>
>>>> - All the hydrogens atoms are not present in your molecule; you
>>>> first need to
>>> add these (4) hydrogens; you could either use xLEaP or R.E.D. Server:
>>>> See http://q4md-forcefieldtools.org/REDS/faq.php#20
>>>> I do not understand how you can end up with atomic charge values in
>>>> this mol2
>>> (output) file without all the hydrogen atoms in the P2N input file...
>>>>
>>>> - The residue name is not correct in your P2N file; May-be Ante_R.E.D. 2.0
>>> does not correct this problem; our new R.E.D. version does.
>>>> Correct that manually; i.e. replace the column '2' by 'CIT' for
>>>> instance.
>>>>
>>>> - Chemical equivalencing is correct in this P2N file; Indeed, here the two
>>> CH2-COO(-) should be equivalent; this means they should bear the
>>> same name two
>>> by two (2 CH2 groups equivalent and 2 COO(-) equivalent). See
>>> http://q4md-forcefieldtools.org/REDS/popup/popanteredtopequiv.php
>>> Our new R.E.D.
>>> version handles that even more automatically; no more P2N files.
>>>>
>>>> - The number of geometrical constraints should be kept as small
>>>> as possible;
>>> for sure if you constraint all the dihedrals of citrate you will
>>> get the same
>>> structure than the experimental one... please read Cieplak et al.:
>>>> http://www3.interscience.wiley.com/cgi-bin/abstract/109583237/ABSTRACT
>>>>
>>>> - No need to use Antechamber here:
>>>> - & no need to convert a mol2 file into a prep file; please read:
>>>> http://q4md-forcefieldtools.org/Tutorial/leap-mol3.php
>>>> mol3/mol2, off, prep file formats have all the same role: to be a
>>>> FF library
>>> file format.
>>>> - atom types can be easily added in the .mol2 file (simply replace
>>>> the chemical symbol by the atom types)
>>>> See http://q4md-forcefieldtools.org/Tutorial/leap-mol2.php
>>>> & more $AMBERHOME/dat/leap/parm/parm99.dat
>>>> CT 12.01 0.878 sp3 aliphatic C
>>>> C 12.01 0.616 sp2 C carbonyl group
>>>> H1 1.008 0.135 H aliph. bond. to C with 1
>>>> electrwd. group
>>>> HO 1.008 0.135 hydroxyl group
>>>> O2 16.00 0.434 carboxyl and phosphate group
>>>> oxygen OH
>>> 16.00 0.465 oxygen in hydroxyl group
>>>> O2 16.00 0.434 carboxyl and phosphate group oxygen
>>>>
>>>> .<TRIPOS>ATOM
>>>> 1 C -0.898932 -1.107716 -0.639849 CT(**) 1 CIT
>>> -0.6640(*)
>>>> 2 C11 0.124175 -0.058604 -0.153210 CT 1 CIT
>>>> 1.0748 3
>>> O 0.288277 -0.676295 1.120574 OH 1 CIT -0.6454 4 H
>>> -0.225218 -0.096106 1.683964 HO 1 CIT 0.3167 5 C10
>>> 1.354615 -0.039384 -1.034103 CT(**) 1 CIT -0.6640 6 C9
>>> 2.555128 -0.398100 -0.207257 C 1 CIT 0.8603 7 O8
>>> 3.121069 0.560707 0.344407 O2 1 CIT -0.8120 8 O7
>>> 2.917251 -1.585703 -0.258239 O2 1 CIT -0.8120 9 C6
>>> -0.351104 1.439904 0.084007 C 1 CIT 0.7813
>>>> 10 O5 -0.304156 2.223542 -0.859272 O2 1 CIT
>>>> -0.8360
>>> 11 O4 -0.716263 1.660876 1.251928 O2 1 CIT
>>> -0.8360 12 C3
>>> -2.294391 -0.800455 -0.184173 C 1 CIT 0.8603 13 O2
>>> -2.914347 -0.237493 -1.108215 O2 1 CIT -0.8120 14 O1
>>> -2.730798 -1.210354 0.899260 O2(!) 1 CIT -0.8120
>>>>
>>>> (*) re-derive the atomic charge values with hydrogen atoms...
>>>> (**) hydrogen atoms of the methylene groups are missing; they
>>>> should bear the
>>> H1 atom type...
>>>> (!) our new R.E.D. version performs atom typing automatically...
>>>>
>>>> If I dare (no offense): better understanding what one does
>>>> instead of using
>>> programs like black boxes without understanding what one does & why...
>>>>
>>>> regards, Francois
>>>>
>>>>
>>>>> I am using angle constraints on the citrate anion (-3) based on the X-ray
>>> data.
>>>>> I have attached the P2N file and the .mol2 file. After optimization, I a
>>> conformation very similar to the experimental conformation. It would
>>>>> be great if
>>>>> you take a quick look through them and let me know if I am making some
>>> obvious/conceptual mistake.
>>>>> Also I am using antechamber to generate the prep and frcmod file
>>>>> for the ion
>>> using the following command:
>>>>> antechamber -i *.mol2 -fi mol2 -o *.prep -fo prepi -nc -3 -j 5
>>>>
>>>>>> Dear Moitrayee,
>>>>>>> We do have an electron density in the crystal structure to which the
>>>>>>> citrate was
>>>>>>> modeled. But I am not sure what sort of experimental data you
>>>>>>> are referring
>>> to.
>>>>>>> It would be immensely helpful if you please elaborate a little
>>>>>>> more so that
>>> I
>>>>> can speak to my experimental collaborator on this issue.
>>>>>> I would simply check that the structure obtained after geometry
>>>>>> optimization
>>> is 'similar' to the experimental one. If not, a
>>>>>> variation of the
>>>>> whole molecule approach (described in the previous email) could be to use
>>> dihedral constraint(s) (a minimum number of constraints) to match the
>>> experimental conformation.
>>>>>> You could use R.E.D. Server to perform geometry optimization
>>>>>> with dihedral
>>>>> constraints from a P2N file;
>>>>>> See
>>>>>> http://q4md-forcefieldtools.org/Tutorial/Tutorial-1.php#CONSTRAINT
>>>>>> If
>>> you do so, please select Gaussian version 2003 because the format of
>>>>> constraints has changed in Gaussian 09 C.01.
>>>>>> regards, Francois
>>>>>>>>> I am performing a MD for which I would require citrate ion (-3)
>>> parameters. It
>>>>>>>>> would great if someone could help me with finding if there are
>>>>>>>>> published
>>>>> citrate
>>>>>>>>> ion parameters. I have searched the AMBER archive but did
>>>>>>>>> not get them.
>>>>>>>> Citrate is a complex case; this is small molecule with 3 negative
>>>>>>>> charges...
>>>>> If you decide to derive charges for the whole molecule, the
>>>>>>>> conformation obtained after geometry optimization is unlikely to be
>>>>> representative of what you want...
>>>>>>>> If you decide to follow the building block approach (see
>>>>>>>> http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php#17) the
>>> constraints
>>>>> used during charge derivation are likely to strongly affect the fit...
>>>>>>>> Do you have experimental data about citrate that could be used to
>>>>>>>> guide the
>>>>> charge derivation procedure?
>>>>>>>> regards, Francois
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Received on Thu Feb 28 2013 - 22:30:04 PST
