VMD-L Mailing List

From: Mayne, Christopher G (cmayne2_at_illinois.edu)
Date: Tue May 19 2015 - 15:07:21 CDT

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 <bennion1_at_llnl.gov<mailto:bennion1_at_llnl.gov>>:
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 cgenff.paramchem.org<http://cgenff.paramchem.org/> 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: owner-vmd-l_at_ks.uiuc.edu<mailto:owner-vmd-l_at_ks.uiuc.edu> [owner-vmd-l_at_ks.uiuc.edu<mailto:owner-vmd-l_at_ks.uiuc.edu>] on behalf of Evandro Semighini [epsemighini_at_gmail.com<mailto:epsemighini_at_gmail.com>]
Sent: Tuesday, May 19, 2015 6:06 AM
To: vmd-l_at_ks.uiuc.edu<mailto:vmd-l_at_ks.uiuc.edu>
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