VMD-L Mailing List

From: Yarrow Madrona (amadrona_at_uci.edu)
Date: Mon Apr 22 2013 - 14:10:18 CDT

Hi Axel,

Thank you for your help. I have been learning MD for only a month now so
please bare with me. I apologize in advance for this long winded post.
Unfortunately, I do not know anyone who has done extensive simulations
with cysteine HEME linkage using CHARM parameters. The few I see on line
look similar to what I have done but I have no way of knowing whether they
see flex in the heme or not.

1. To answer your first question: The first simulations were done with the
top_par_22_heme.str streaming file that is input into NAMD. I had the same
problems with some non-planarity. kind of looks like a v with the iron at
the apex (about 150 to 160 deg). There was also a distance contrain
between the cysteine and iron.

I have heard in a forum that for a pentacoordinate heme like Myoglobin
with Histine coordinating it is better to use the PHEM; His bound to Fe
patch in the heme streaming file. It was mentioned that the "The FHEM
patch is needed to remove a couple N-Fe-N ANGLE terms added by
(AUTO)GENERATE". See
http://www.charmm.org/ubbthreads/ubbthreads.php?ubb=showflat&Number=25711

I was having a little difficulty understanding how to implement the
patches so I built the parmameter file/topology file for a HEME + Cystene
residue I called HEC. I defined bonds, Improppers and internal
coordinates in the topology file. Most of these come straight from the
HEME streaming file with corrections for the new cysteine bond. I also
entered the spring constant, distance and angle in the parameter file.
Everything behaves well except for that that flexing of the Heme.

The only thing that is not in there from the heme streaming file is the
following:

DELETE ANGLE 2NA 2FE 2NC 2NB 2FE 2ND
ANGLE 1C1 1S 2FE 1C1 1S 2FE
ANGLE 1S 2FE 2NA 1S 2FE 2NB 1S 2FE 2NC 1S 2FE 2ND
IC 1C1 1S 2FE 2NA 0.0000 0.0000 0.0000 0.0000 0.0000
IC 1C1 1S 2FE 2NB 0.0000 0.0000 0.0000 0.0000 0.0000
IC 1C1 1S 2FE 2NB 0.0000 0.0000 0.0000 0.0000 0.0000
IC 1C1 1S 2FE 2NB 0.0000 0.0000 0.0000 0.0000 0.0000

I added the IC's to the parameter file but it does not seem to make a
difference. I suppose I can add the delete comment into the psfgen before
running it. Should I manually put in the length, dihedral and angle of
all of the above?

I already have defined may of them in addition to the ones taken from Heme
streaming file:

IC -C CA *N HN 1.3479 123.9300 180.0000 114.7700 0.9982
IC -C N CA C 1.3479 123.9300 180.0000 105.8900 1.5202
IC N CA C +N 1.4533 105.8900 180.0000 118.3000 1.3498
IC +N CA *C O 1.3498 118.3000 180.0000 120.5900 1.2306
IC CA C +N +CA 1.5202 118.3000 180.0000 124.5000 1.4548
IC N C *CA CB 1.4533 105.8900 121.7900 111.9800 1.5584
IC N C *CA HAY 1.4533 105.8900 -116.3400 107.7100 1.0837
IC N CA CB SG 1.4533 111.5600 180.0000 113.8700 1.8359
IC SG CA *CB HB1 1.8359 113.8700 119.9100 107.2400 1.1134
IC SG CA *CB HB2 1.8359 113.8700 -125.3200 109.8200 1.1124
IC CA CB SG FE 1.5584 113.8700 180.0000 111.5140 2.2000

Thank you.
-Yarrow

> two comments:
> 1) have you made some test calculations with the regular heme residue as
provided in the parameter set to have a reference to compare to? 2)
parts of molecules are usually held flat through improper
> dihedrals. have you checked whether they are exist where needed and have
assigned parameters for your custom residue? again, it can be extremely
helpful to compare to "vanilla" reference.
> axel.
> On Mon, Apr 22, 2013 at 12:49 AM, Yarrow Madrona <amadrona_at_uci.edu>
wrote:
>> Hello,
>> I know this is a CHARMM question but I am having trouble finding
information on this.
>> I am wondering if anyone here has experience with HEME-cystiene Fe
thiol
>> or Fe-HIS simulation. I recently build a parameter and top file with a new
>> residue "HEC" which is a combination of the HEME and cysteine as a single
>> residue. I took most of the HEME parameters from the CHARMM Heme streaming
>> toppar file.
>> Everything looks fine except the HEME seems to flex a little. Looks a
little like a "V" Maybe 140-160 deg instead of 180 degrees across the
heme. I have heard that there are some parameters to take from the PRES
SUL patch in the HEME topar streaming file. I have taken and modified
the
>> relevant ones but I was wondering if anyone knows specifically, what would
>> cause the heme to be less than ideal planar.
>> Thank you for your help.
>> --
>> Yarrow Madrona
>> Graduate Student
>> Molecular Biology and Biochemistry Dept.
>> University of California, Irvine
>> Natural Sciences I, Rm 2403
>> Irvine, CA 92697
> --
> Dr. Axel Kohlmeyer akohlmey_at_gmail.com http://goo.gl/1wk0
> International Centre for Theoretical Physics, Trieste. Italy. 

-- 
Yarrow Madrona
Graduate Student
Molecular Biology and Biochemistry Dept.
University of California, Irvine
Natural Sciences I, Rm 2403
Irvine, CA 92697