AMBER Archive (2004)

Subject: RE: AMBER: MD simulation : problem

From: Ross Walker (ross_at_rosswalker.co.uk)
Date: Mon Jul 12 2004 - 12:55:33 CDT

Hi Sachin,
 
First of all a couple of things that I don't know if are due to a typo in
your message below. ntb:
 
ntb = 0 (NO periodic boundaries - don't use this if you have solvate with a
BOX of water)
 
ntb = 1 Periodic boundaries (PME) constant volume. Use when minimising and
initally heating / equilibrating your system.
 
ntb = 2 Periodic boundaries (PME) constant pressure. Use for a production
run once you have heated and equilibrated at constant volume.
 
Your message seems to suggest that you don't get any output when ntb>0. I.e
when periodic boundaries are turned on. This is not good and suggests that
you may have a problem with your amber installation (although you don't
specify how long you let the job run for, with buffered output it can
sometimes be a while before anything is written to the output file). I would
make sure you run the test cases and check they complete successfully.
 
Now, on to the simulation. what I would do is as follows...
 
1) Take your gas phase pdb initial structure and manually work out where you
want the initial water molecules to be. Then manually add these, say 3 or 4
water molecules, to the pdb file with residue name WAT.
 
2) Visualise this structure and check the water molecules are in a
reasonable position in the binding site.
 
3) Minimise this system (ca. 500 steps) in gas phase with large cut off and
ntb = 0. This step may not be necessary depending on how well you placed the
water molecules... Check the structure after minimisation to see if it is
still reasonable... ambpdb -p prmtop <restrt >minimised.pdb
 
4) Load the minimised pdb into leap, charge neutralise and then solvate with
TIP3P water:
 
solvate unit TIP3PBOX 10.0
 
Check how many water molecules this adds and thus the total number of atoms
in your system. Note, if you have more than 20,000 atoms or so you are
likely to have a hard time on a single cpu machine. I recommend running on a
cluster of 4 or 8 cpus at least...
 
5) Minisize the system in two stages, water first with 'weak' restraints on
protein. Then entire system...
 
6) Heat from 0 to 300K with ntb=1 and ntt=3, gamma_ln=1.0, over about 20ps
or so... ntx=1, irest=0
 
7) switch to ntb=2 and run production md (ntx=5, irest=1 and give it the
restrt file from 6 as the coords -c restrt) for as long as you need with
tempi=300 and temp0=300, ntt=3 and gamma_ln=1.0. Note, depending on the
timescales of what you hope to see you may need to dump to the mdcrd file
fairly regulary, say every 50fs or so, ntpr=50,ntwx=50 (note it will get
VERY BIG, if it exceeds 2GB you will probably need to split your sim into
several stages).
 
8) Take a look at the results...
 
Note, if your system starts blowing up, which it may well do then you will
need a much more elaborate minisation and equilibration scheme...
 
I hope this helps.
All the best
Ross
 
/\
\/
|\oss Walker

| Department of Molecular Biology TPC15 |
| The Scripps Research Institute |
| Tel:- +1 858 784 8889 | EMail:- ross_at_rosswalker.co.uk |
| http://www.rosswalker.co.uk/ | PGP Key available on request |

  _____

From: owner-amber_at_scripps.edu [mailto:owner-amber_at_scripps.edu] On Behalf Of
sachin patil
Sent: 11 July 2004 21:54
To: amber_at_scripps.edu
Subject: RE: AMBER: MD simulation : problem

Hi Ross,
Actually I am trying to see whether water molecules play a role in binding
interaction of the ligand with the receptor in my system. I dont know
whether there exists any way by which I can add water molecules selectively
at the ligand binding site. So that, I can see whether the water molecules
move in to the ligand binding groove and take part in the binding
interaction.

 Hence I added a water cap by eyeballing the coordinates of my ligand. ( as
mentioned in the Streptavidin-Biotin tutorial).But my problem is I dont know
what kind of setup should I use for MD simulations. I am using Redhat Linux
on AMD Athlon processor Following is my input file-

 heating up the system equilibration stage 1

&cntrl

irest=0,

 ntx=1, tempi=100.0, ntt=1,

temp0=300.0, tautp=2.0, ntp=0,ig=209858,

nstlim=500,dt=.002,

ntc=2, ntf=2,ntwr=500,

ntpr=20, ntwx=500,

nrespa=2,

&end

What I mean by "I tried to run the simulation with periodic boubdary
conditions as above (cutoff 12.0) but the system just doesn't go anywhere."
that that sander fails to write any output to the md.out file ( it remaims
empty). Even in the energy minization steps I have to use ntb=1.

Interestingly, when I turn on the periodic boundary conditions (ntb=0) then
the simulation runs fine. So my problem is how do I add water molecules
selectively and the binding site? If there is any way to do this then shall
I run the simulations with periodic or non-periodic conditions?

 

Thanks in advance

Regards

Sachin Patil

------------

Dept. of Medicinal & Biological Chemistry

Univ. of Toledo Toledo, Ohio, 43606

Ross Walker wrote:

Dear Sachin,

If you are trying to observe the movement of the water molecules you are
unlikely to learn much bu having a water cap of jut 32 water residues. The
reason for this is that the outer water molecules of the cap has a
restraining force that acts to keep them as part of the water cap and so
stop them boiling off into vacuum. With only 32 water molecules in the cap a
large proportion are going to be restrained and so the movement of the water
molecules is going to be un-representative of a bulk system.

I'm not sure what you mean by the statement "I tried to run the simulation
with periodic boubdary conditions (cutoff 12.0) but the system just doesn't
go anywhere."

Are you implying it runs very slowly (what computer spec do you have and how
big is your system) or that something is wrong with the MD. Ideally if you
can afford it you want to run periodic boundary conditions with your entire
system solvated in a box of water. Typically you want a buffer size of at
least 10A around the entire protein. If you cannot afford such an expensive
calculation then try a solvent cap or implicit solvent but be aware of the
limitations. Especially with regard to things being restrained in the
solvent cap case.

I hope this helps.
All the best
Ross

/\
\/
|\oss Walker

| Department of Molecular Biology TPC15 |
| The Scripps Research Institute |
| Tel:- +1 858 784 8889 | EMail:- ross_at_rosswalker.co.uk |
| http://www.rosswalker.co.uk/ | PGP Key available on request |

  _____

From: owner-amber_at_scripps.edu [mailto:owner-amber_at_scripps.edu] On Behalf Of
sachin patil
Sent: 11 July 2004 08:08
To: amber_at_scripps.edu
Subject: RE: AMBER: MD simulation : problem

Hi Ross,
Thank you for you suggestions. It really helps a lot.
Actually, I have solvated my system with a water cap (32 water residues) and
I am trying to see the movement of the water molecules.
I tried to run the simulation with periodic boubdary conditions (cutoff
12.0) but the system just doesn't go anywhere. So I switched to nonperiodic
conditions as mentioned
in the Streptavidin Biotin tutorial.
But my problem was that I was not sure whether I am correct in using
non-periodic
conditions for my system.
So my questions is how do one selectes whether he should use periodic or
non-periodic conditions for his system?

Thank you again
Regards
Sachin Patil
-----------------
Dept. of Medicinal & Biological Chemistry
University of Toledo, Toledo
Ohio 43606

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