From: Evandro Semighini (
Date: Thu Jun 25 2015 - 14:28:21 CDT

Hello again,

I managed to answer some of my previous questions, but now I got into
others, which I will appreciate if you could help me again.

The issues about Gaussian were in my computers/license. Using Gaussian 9 in
another machine I managed to run the calculations in an appropriate time.

But, following the recommendations from Brian Bennion and Christopher Mayne
(here and at NAMD list), and reading all I could find in VMD list about
fftk, and also the Mackerell slideshow from the tutorial, I got stuck at
the next step.

1- I need to run the Gaussian water interactions with the whole molecule or
I can run only the ones from the region with high penalty from the
2- Considering that my molecule has 4 parts, A-B-C-D, I must split it in A,
B, C and D parts or A-B, B-C and C-D to run the optimizations ?
If the answer is in individual parts, to get the right charges I just need
to sum the charges from the bonding ones and the hydrogens that replaces
the "next atom" at the split ?
If the answer is in pairs, how I get the correct charges for the atoms
common to the pairs ?
3- I must perform the optimization first in simulated annealing, save the
log and then re-run the optimization with the downhill method, at FFTK ?
I made it first with downhill and the charges were the same from the
Paramchem, but with sim_an, followed by downhill, the charges were
different, some by more than 0.2.
4- Not all of my molecules got high penalties (some got none) from
PARAMChem. To obtain a more standard result from all my MDs, I need to
parameterize them with gaussian too ?

Sorry for some questions, but I got suspicious with easy answers.

Thank you all in advance.

Evandro Semighini

2015-05-19 17:07 GMT-03:00 Mayne, Christopher G <>:

> Evandro,
> Please note that parameterization is an advanced topic, even for
> experienced practitioners of molecular dynamics. I strongly suggest that
> before jumping into parameterizations of large, complex molecules, that you
> first work through parameterizations of smaller, simple molecules to gain a
> better understanding of the force field, and the more importantly, the
> established protocols for parameterizing for that force field. These
> protocols are not arbitrary, and deviations from them should be well
> thought out and justified to obtain reasonable and reliable results.
> In addition to Brian's response I'll add that:
> One of the key ways in which CHARMM is different from GROMOS and AMBER
> is the method for developing charges. The CHARMM protocol is founded on
> optimizing water interactions, which is critical to maintain compatibility
> with other CHARMM force fields (e.g., biopolymers, CGenFF). The charges
> returned by the QM software are computed by different methods that are
> (potentially) more meaningful to the QM calculation than any subsequent
> MM-based MD calculation.
> Regards,
> Christopher Mayne
> On May 19, 2015, at 12:45 PM, Evandro Semighini wrote:
> Hello Brian,
> Thanks again !
> 1- I read it and saw the difference between the force fields that was
> confusing me, but a friend of mine, that works with GROMACS and AMBER FF,
> told me to try the chelp charges.
> 2 an 3- God point, got it.
> 4- I got the files generated from fftk, it takes at least 3 hours for
> every run with one processor (with more, it crashes) in an Intel Core i3
> 2100 processor.
> Unfortunatelly, the last advice will be the hardest part to get. =/
> Thank you Brian !
> Evandro
> 2015-05-19 12:51 GMT-03:00 Bennion, Brian <>:
>> Hello,
>> Please read Dr. Mayne's paper that describes ffTK, it will provide
>> insight on question 1 (ie how charges are determined for the charmm
>> forcefield).
>> Question 2. It is up to you to decide if the penalties given by
>> are worth worrying about. If someone needed to
>> repeat your work and they parameterized everything de novo, would you trust
>> their results if they differed from your results?
>> Question 3. If you don't optimize the bonded parameters then you get
>> what the cgenff forcefield supplies (or doesn't supply for that matter).
>> The forcefield has NO idea that your compound needs to be "frozen" in that
>> docked conformation, unless you tell it by giving it the appropriate
>> parameters. Please realize that the docked conformation represents a
>> theoretical complex at 0 Kelvin. Will you or others do the experimental
>> studies at 0 Kelvin?
>> Question 4. It depends if you are running he calculation correctly or if
>> your hardware/software is properly setup for these calculations.
>> These questions point out that you need to do some more reading and ask
>> for guidance from your mentor/supervisor.
>> Sincerely
>> Brian Bennion
>> ------------------------------
>> *From:* [] on behalf of
>> Evandro Semighini []
>> *Sent:* Tuesday, May 19, 2015 6:06 AM
>> *To:*
>> *Subject:* vmd-l: Questions regarding fftk and Gaussian
>> Hello VMD community !
>> I'm new to NAMD and VMD and have some questions about the
>> parameterization of the molecules I got from virtual screening assays.
>> I got a huge help from the NAMD mailing list and it leaded me to another
>> kind of problems and doubts, regarding fftk and Gaussian, that I was unable
>> to solve by myself/searching, so, here I am.
>> I was instructed by mrs. Crystopher Mayne and Brian Bennion to use
>> ParamChem and then cut the molecules in pieces with molefracture to
>> optimize them with fftk and Gaussian, and there's where I am stuck now.
>> As my molecules are sort of big, fftk creates more than 90 water
>> interaction files to be loaded to Gaussian for each one, and I have more
>> than 30 molecules.
>> 1- Do I really need to run all of this water optimization in Gaussian
>> or I can run just the geometry optimization, which calculates new charges ?
>> 2- If no, can I run only the interactions for the highest penalized atoms
>> or, there is other method with lower time cost ?
>> 3- Do I really need to optimize the angles and dihedrals penalties, as
>> my molecules are in the docked conformation ?
>> 4- I never used quantum softwares before, so, is it normal this
>> calculations take several hours to end ?
>> Thank you in advance for any help.
>> Evandro Semighini