AMBER Archive (2009)

Subject: Re: [AMBER] Creating conditions for biased MD

From: Francesco Pietra (chiendarret_at_gmail.com)
Date: Tue Apr 21 2009 - 13:40:35 CDT

On Mon, Apr 20, 2009 at 8:46 PM, Carlos Simmerling
<carlos.simmerling_at_gmail.com> wrote:
> I think it might be easier with dihedral angle restraints. it depends
> on the rest of the system- if it's just the one helix, you could use
> the impose command in leap to make a continuous helix as a reference
> for SMD.

I begun from the last suggestion, recreating the protein (made of
capped helices which had been before isolated from the whole protein),
with commands "model1 = loadpdb" "model2 = load pdb" (where the two
models had been aligned before) and "model3 = combine" the protein
was inserted into a lipidic membrane.

Then command

impose model3 { 225 226 227 228 229 230 } { { "N" "CA" "C" "N"
-40.0 } { "C" "N" "CA" "C" -60.0 } }

Then, with command "solvatebox" it was hydrated. The prmtop and inpcrd
opened in a viewer, WAT and lipid removed, the bent helix looks like
(grossly) unaffected. The bending angle is still ca 40 degrees.

Should straightening of the helix have been expected at this stage or
the impose command will be felt on running MD simulations? Or, have i
misunderstood everything?

thanks for having a look at this message

francesco

>
>
>
> On Mon, Apr 20, 2009 at 1:31 PM, Francesco Pietra <chiendarret_at_gmail.com> wrote:
>> Carlos: late in thanking you. I had to fix hardware and software problems.
>>
>> Complex:
>>
>> phi Gly227C  Gly228N  Gly228CA Gly228C  ca 78 degrees (positive)
>>
>> psi Gly228N  Gly228CA  Gly228C  Gln229N  -19 degrees
>>
>> In a cartoon view, two cylinders make an angle of ca 40 degrees,
>> interconnected by 227 228. I would like to approximately straighten
>> that, to get a continuous cylinder. In a helix view, phi should be
>> turned anticlockwise to reach at least the value -80 degrees (the
>> value of corresponding nearby dihedral is just -80 degrees, while
>> farther away it takes normal values, -57 degrees). psi, at least, has
>> the correct sign.
>>
>> The bent helix is capped on both sides, but there are other similar,
>> capped helices around, so that I guess the work should be carried out
>> on the whole model. If I could restrain the capping groups alone of
>> the bent helix (while finding a way that helicity, where correct, is
>> conserved) I could imagine that straightening could occur. Otherwise,
>> if all amino acids, except 227 228 of the bent helix, are restrained,
>> how could the helix get straightened? Is that a task for SMD at all?
>>
>> thanks
>> francesco
>>
>>
>>
>>
>> On Mon, Mar 30, 2009 at 1:56 PM, Carlos Simmerling
>> <carlos.simmerling_at_gmail.com> wrote:
>>> francesco, I think dihedral restraints may be the only way to go without a
>>> helical ref structure. you'd definitely want to also restrain all other
>>> residues in this helix to maintain it, or else you might just move the bend.
>>> when changing the restraints over time, give thought to which direction to
>>> rotate, which depends on the initial conformation of the Gly residues, if
>>> they are currently adopting positive phi values then it's more complex than
>>> just going from pp2 to alpha, for example, where you can just reduce psi.
>>>
>>> On Mon, Mar 30, 2009 at 6:16 AM, Francesco Pietra <chiendarret_at_gmail.com>wrote:
>>>
>>>> Hi:
>>>> I would like to modify the conformation of a protein at one helix,
>>>> which is bent at a region of three amino acids, Ile, Gly, Gly. Viewed
>>>> in cartoon representation, it is constituted of two straight portions
>>>> interconnected through a largely non helical set of the three amino
>>>> acids.
>>>>
>>>> I would appreciate suggestions how to get the three aa taking part to
>>>> the well ordered helical conformation, so that what is now (in
>>>> cartoon) two straight portions interconnected by something like a loop
>>>> becomes a wholly straitened motif. Rotation about dihedrals? Make the
>>>> process with the isolated helix or in the whole context of the
>>>> protein?
>>>>
>>>> I guess that steered MD (on which I have no experience) is the
>>>> approach in Amber, though I wonder how to provide the target.
>>>> Possibly, any biased MD should be carried out in explicit medium. In
>>>> my hands, continuum models were unsuccessful with this protein.
>>>>
>>>> If these are not such naive questions to merit attention, thanks
>>>>
>>>> francesco pietra
>>>>
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