From: Daan Mevius (daanmevius_at_gmail.com)
Date: Sun Oct 11 2015 - 06:20:19 CDT

Hello,

I want to do Molecular Dynamics on Histone methyltransferase enzymes which
require the S-Adenosyl-L-methionine / SAM co-factor. Therefore I have to
generate correct Topology & Parameter files. However this has proven to be
problematic for me. Similar questions about this compound have come up
before and have been solved. However I still did not manage to successfully
run my MD simulations.

The SAM compound contains a cationic tricoordinate Sulphur which creates
problems for Topology & Parameter generators such as CGenFF, Paramchem,
SwissParam, Charmm-gui and PSFgen. All of these run into errors and do not
provide me with correct output files.

There is one paper which generously provides their Topology & Parameter
files:

‘’Insight into Enzymatic C−F Bond Formation from QM and QM/MM Calculations
by Hans Martin Senn
<http://pubs.acs.org/action/doSearch?ContribStored=Senn%2C+H+M> ,*
<http://pubs.acs.org/doi/suppl/10.1021/ja053875s#ja053875sAF1>†
<http://pubs.acs.org/doi/suppl/10.1021/ja053875s#ja053875sAF2> David O'Hagan
<http://pubs.acs.org/action/doSearch?ContribStored=O%27Hagan%2C+D> ,‡
<http://pubs.acs.org/doi/suppl/10.1021/ja053875s#ja053875sAF3> and Walter
Thiel <http://pubs.acs.org/action/doSearch?ContribStored=Thiel%2C+W> *
<http://pubs.acs.org/doi/suppl/10.1021/ja053875s#ja053875sAF1>†
<http://pubs.acs.org/doi/suppl/10.1021/ja053875s#ja053875sAF2>; *J. Am.
Chem. Soc.*, 2005, 127 (39), pp 13643–13655 *DOI:* 10.1021/ja053875s’’ (
http://pubs.acs.org/doi/suppl/10.1021/ja053875s)

With this topology file I am able to create a PSF file without any apparent
errors (There might be a problem while creating this however, I am not sure
about this), followed by the creation of a waterbox. However when I try to
run Energy Minimization & Molecular dynamics using NAMD (using script or
VMD graphical interface) I run into the same errors:

Info: USING ARITHMETIC MEAN TO COMBINE L-J SIGMA PARAMETERS

Warning: DUPLICATE ANGLE ENTRY FOR CPH1-NR1-CPH2

PREVIOUS VALUES k=130 theta0=107.5 k_ub=0 r_ub=0

   USING VALUES k=130 theta0=107 k_ub=0 r_ub=0

FATAL ERROR: UNKNOWN PARAMETER IN CHARMM PARAMETER FILE
C:/Users/Daan/Documents/PhD-KNU/Correct-AdoMet/AdoMet-paper-parameters-auto.par

LINE=*CN8B S 240.000 1.858 !hms: r0 from QM(aq)*

I included the NAMD input file and NAMD output files in the attachments in
txt format.

I have seen in the other posts that it might have something to do with the
AUTOgeneration of angles and/or dihidrals, but all I have been able to find
is the following command:

AUTOgen { ANGLes [ DIHEdrals ] }

          { DIHEdrals [ ANGLes ] }

It has also been mentioned that these files can be created using ADE, and
the SAM Patches using the toppar files. However since my knowledge about
this topic is limited i have unfortunately not been able to get this
working.

I have tried many things but have not been able to solve this problem for
over a week. If someone here would be willing to help me that would be
great! Thank you in advance, Daan Mevius.