Re: Protein-ligand simulation

From: James Starlight (
Date: Tue Jun 25 2013 - 00:58:51 CDT

Hi Kenno,

thanks for such detailed explanation!

Today I've used CGenFF at for my test molecule (negatively
charged cyclic guanosine mono phosphate). As the result I've obtain big
penalties for some charges as well as angles and dihedrals. Does it mean so
I should refine this topology by means of FFTK for instance ? On what
refinement steps should I pay more attention ?
How should I convert CGenFF output (str file) to the Namd par format ?

Thanks again for help,


RESI tmp2.pdb -1.000 ! param penalty= 196.000 ; charge penalty= 111.390

2013/6/25 Kenno Vanommeslaeghe <>

> Hi Guys,
> Allow me to add some background info:
> There is parameter *assignment*, which takes less than a second and during
> which the computer basically makes an educated guess at what would be good
> parameters, typically based on similarities between the ligand and existing
> molecules in the force field. For the specific case of CHARMM, I know of 3
> interfaces that do so:
> * SwissParam
> * the CGenFF program at
> * MATCH from the Charlie Brooks lab
> Out of these three, I recommend *against* SwissParam because it's based on
> an unfortunate mixing between MMFF94 parameters and CHARMM parameters, as
> discussed on a few occasions on the CHARMM forums. Also, since I wrote the
> CGenFF program, I'm obliged to say that CGenFF is da best(*) :)
> Then there is parameter *optimization*, which typically takes the output
> of the above parameter *assignment* as an initial guess, and refines it
> using QM and experimental target data. FFTK is an example of the latter -
> there exist others as well.
> Putting this together in a NAMD context, present-time best practice would
> probably be to feed your ligand to the CGenFF program at ,
> then if there are high penalties (which is more often the case than not)
> feed the results to FFTK. Among other advantages, this course of action
> allows you to avoid the tedious and error-prone "System Preparation II:
> Setting NONBONDED Parameters By Analogy" step in the FFTK tutorial. Indeed,
> the CGenFF atom typing rules have become unusually complex, with many
> exceptions, and I currently have more faith in the CGenFF program's ability
> to assign correct atom types than in any human being (including myself and
> Alex MacKerell).
> Cheers,
> Kenno.
> (*) Just kidding. To be serious, there does not yet exist an independent
> comparative study on full-sized drug-like molecules showing the strengths
> and weaknesses of CGenFF vs. MATCH, but I'm looking forward to it. What
> speaks in favor of CGenFF right now is:
> * it's the reference implementation of the CGenFF atom typing rules
> * broader support for linkages between functional groups
> On Jun 24, 2013, at 7:55 PM, JC Gumbart wrote:
>> Clearly FFTK. :)
>> On Jun 24, 2013, at 2:15 PM, James Starlight wrote:
>>> Chris, thanks you! I'll be very thankful for your tutorial!
>>> By the way what is the current most useful way to obtain charm
>>> parameters for small ligand-like compounds (starting from its full atomic
>>> pdbs with hydrogens) ?
>>> With Gromacs (using charm36 force field) typically I use swiss-param
>>> server which also produce PRM files in addition to the gromacs topology.

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