AMBER Archive (2008)

Subject: AMBER: RE: amber tutorial A3

From: Ross Walker (
Date: Tue Apr 22 2008 - 23:45:29 CDT

Hi Sean,
I'm an undergraduate student at St. Olaf College in Northfield, MN, USA. The class I'm currently taking, biophysical chemistry, has a research project component, and our professor recently acquired Amber 9 for college use. A couple of us began to explore a couple weeks ago the general structure of the software by going through a couple tutorials, and I'm particularly interested in the applications for MD in medicinal chemistry. Needless to say, I went right for tutorial A3 with the Ras-raf protein complex. I found it very interesting and informative, and was able to get values similar to yours for the free energy of binding.

I'd like to further explore the effect of urea on the free energy of binding, and I was able to solvate the complex in tleap using the predefined solvent. However, I'd like to investigate the effect of smaller concentrations of urea. Is there a good way to change a couple of the urea residues in the box to water residues, to lower the concentration? Thanks for your help and consideration!

My apologies for not replying sooner - I have been travelling a lot of late. I am copying this message to the amber mail reflector since this is the best place for these types of questions as others can learn from this response. See for signup details.
I am glad you liked the tutorials.
As for making a different urea concentration I have never tried this myself although it shouldn't be too hard to do - although may involve a bit of effort. I would start by taking the 8M urea box. I can think of a number of ways to do this some which will likely be more efficient than others.
However, one approach that springs to mind (that I think will work okay) is to start with a box of urea in leap. Just have leap copy the existing urea box.
foo = copy urea (or whatever the urea box unit is called).
This will give you a box with a defined number of urea and water residues in it. You'll then need to calculate the number of additional water molecules you'd need to give you the molar concentration you want. Once you have this you can then use the solvatebox command to solvate the urea box (now unit foo) with TIP3PBOX (tip3p water). You can play about with the buffer size to get the number of waters you need. You can just keep making multiple copies of the original urea box - named foo2, 3 etc so you don't have to keep reloading things.
Once you have this correct you should then save yourself a prmtop and inpcrd file. You then need to equilibrate this box to let things mix correctly. So take the prmtop and inpcrd and run yourself several ns of MD - start with minimization, constant volume heating and then constant pressure MD (like in the DNA tutorial) and run it until things are properly mixed - you'll have to think up some objective measure for establishing when things are mixed correctly.
Then once you have this you can use ptraj or ambpdb to make a pdb file of your final restart file. You should (you may need a little tweaking of the pdb naming though) be able to open xleap, load in your protein and then do:
protein = loadpdb protein.pdb
blah = loadpdb final_urea_mix.pdb
that will create the blah unit. You can then do:
solvateoct protein blah 10.0
to add 10 angstroms buffer of your new urea solution around the protein - I think this should work okay. Then you can just add ions as necessary and do saveamberparm protein foo.prmtop foo.inpcrd and I think you'll be ready to go. As I say this procedure may need a little tweaking but the basic approach should be sound.
I hope this helps,
Good luck,

|\oss Walker

| Assistant Research Professor |
| San Diego Supercomputer Center |
| Tel: +1 858 822 0854 | EMail:- |
| <> | PGP Key available on request |

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