Re: [AMBER] Abasic Site and Leap Polymerization

From: Christina Bergonzo <cbergonzo.gmail.com>
Date: Sat, 4 Apr 2020 17:37:10 -0400

This is not required for the explicit solvent simulations, I just use the right mbondi set for my GB model of choice if I intend to do MMGBSA or some energy decomposition.

-Christina

> On Apr 4, 2020, at 4:01 PM, Robert Molt <rwmolt07.gmail.com> wrote:
>
> ´╗┐Thank you! This is most helpful!
>
> I am inferring that the
>
> set default PBradii mbondi2
>
> engaged Poisson Boltzmann radii for the simulation. Is using a PB implicit solvent requisite for this set of parameters, in terms of compatibility? The article by Case I am using as reference did explicit solvent calculations, such that this seems not rigorously needed?
>
>> On 4/4/20 12:42 PM, Christina Bergonzo wrote:
>> Hello,
>>
>> The ABB.off file is loaded as a library file using the "loadoff" command in
>> leap.
>> The off files contain the same information as .lib files (atom names,
>> types, charges, coordinates of template).
>> You need to load the off file, and the frcmod file as shown below.
>>
>> Additionally - you will need to modify your PDB file.
>> I am sending you a test.pdb and a test.ABB.pdb with the abasic site
>> incorporated into it, so you can see how the residue is denoted.
>> The files are old so they use outdated PDB naming conventions (for DNA this
>> means switching OP1/OP2 to O1P/O2P, and changing the H5'/'' to H5'1/H5'2
>> and H2'/'' to H2'1/H2'2, though I just delete hydrogens and let leap build
>> them in). You should probably update the atom names if you want to use them
>> without editing PDBs all the time...
>>
>> Leap commands I used here (loading the leaprc necessitates having
>> $AMBERHOME set, and I specify a local path for the abasic site parameters
>> location):
>>
>> source leaprc.DNA.OL15
>> loadoff ~/bin/lib/ABB.off
>> loadamberparams ~/bin/lib/ABD.frcmod
>> mol = loadpdb test.pdb
>> set default PBradii mbondi2
>> saveamberparm mol test.ABB.parm7 test.ABB.rst7
>> savepdb mol test.ABB.pdb
>>
>> Good luck!
>> -Christina
>>
>>> On Sat, Apr 4, 2020 at 11:56 AM Robert Molt <rwmolt07.gmail.com> wrote:
>>>
>>> Good morning fellow Covid-Zombies!
>>>
>>> Drs. Bergonzo and Simmerling: your perspicacity and patience are
>>> appreciated! Thank you!
>>>
>>> I still have some confusions, if I may. I have previously worked with
>>> using modified amino acid residues in a manner very similar to the
>>> tutorial given by
>>>
>>> https://ambermd.org/tutorials/basic/tutorial5/index.htm
>>>
>>> I am extremely appreciative of your frcmod file; you are kind to help a
>>> fellow scientist with no benefit. I am confused on the .off file? What
>>> is its purpose? I am used to prepin files to "inform" how a unit fits
>>> inside a polymerization; is a .off file serving a similar purpose? I
>>> cannot find the term in the manual?
>>>
>>> On 3/30/20 2:21 PM, Christina Bergonzo wrote:
>>>> Hello,
>>>>
>>>> Yes, Carlos is right.
>>>> In your example, you would rename the "48Z" residue in your PDB file as
>>>> "ABB" and then the loaded off and prep files would be used.
>>>> Alternatively, you can rename the library files to match the residue you
>>>> have.
>>>> But by necessity, you'll need to call this something other than DA or DC,
>>>> since leap would just build in those entire nucleobases based on those
>>>> residue names.
>>>>
>>>> -Christina
>>>>
>>>> On Mon, Mar 30, 2020 at 1:14 PM Carlos Simmerling <
>>>> carlos.simmerling.gmail.com> wrote:
>>>>
>>>>> I think Christina was suggesting that you use a new residue name and
>>>>> library, then the base won't get added.
>>>>> Look at this paper for an example
>>>>> Active destabilization of base pairs by a DNA glycosylase wedge
>>> initiates
>>>>> damage recognition
>>>>> Kuznetsov, N. A., Bergonzo, C., Campbell, A. J., Li, H., Mechetin, G.
>>> V.,
>>>>> de los Santos, C., Grollman, A. P., Fedorova, O. S., Zharkov, D. O.,
>>>>> Simmerling, C., Nucleic Acids Research, 2015, 43 (1), 272-281
>>>>> DOI: 10.1093/nar/gku1300
>>>>>
>>>>> On Mon, Mar 30, 2020 at 1:08 PM Robert Molt <rwmolt07.gmail.com> wrote:
>>>>>
>>>>>> Good afternoon,
>>>>>>
>>>>>> I am very appreciative for the parameter suggestion, but unless I am
>>>>>> confused, I do not see that it addresses the question I asked? I am
>>>>>> confused about how to "leave a space" properly, and use the existing
>>>>>> parameters?
>>>>>>
>>>>>> On 3/30/20 11:07 AM, Christina Bergonzo wrote:
>>>>>>> Hello,
>>>>>>>
>>>>>>> In the past (the way past - 2011!) we have used these parameters:
>>>>>>> https://www.ncbi.nlm.nih.gov/pubmed/17323932
>>>>>>>
>>>>>>> Kun Song created these leap files while in Carlos Simmerling's lab.
>>>>>>> I attached the off and frcmod files to this email, as well as a
>>>>> picture.
>>>>>>> Please make sure they are compatible with any changes to the DNA FF
>>>>> since
>>>>>>> 2007!
>>>>>>>
>>>>>>> -Christina
>>>>>>>
>>>>>>> On Mon, Mar 30, 2020 at 10:36 AM Robert Molt <rwmolt07.gmail.com>
>>>>> wrote:
>>>>>>>> Good morning,
>>>>>>>>
>>>>>>>> I am attempting to simulate abasic DNA with a protein "bonded" to
>>> said
>>>>>>>> DNA structure. In particular, an amino acid ends up "occupying" the
>>>>>>>> "empty" location of the abasic DNA.
>>>>>>>>
>>>>>>>> In attempting to figure out the best way to construct this in Amber,
>>> I
>>>>>>>> found the following post:
>>>>>>>>
>>>>>>>> http://archive.ambermd.org/201901/0211.html
>>>>>>>>
>>>>>>>> in which Dr. Case elaborates that one might "remove the base from A,
>>>>>>>> replacing it with a hydrogen."
>>>>>>>>
>>>>>>>> I think I have a misunderstanding of how leap works for which I seek
>>>>>>>> clarification.
>>>>>>>>
>>>>>>>> I have a "residue" named 48Z which is the phosphate backbone in my
>>>>>>>> crystal structure associated with the abasic site. I think I have to
>>>>>>>> "name" this residue something akin to "DA" or "DC" in order to tell
>>>>> leap
>>>>>>>> to connect the phosphate backbone properly (it expects to connect the
>>>>>>>> polymer). But to my understanding, the act of doing so will
>>>>>>>> automatically tell leap to fill in the missing heavy atoms? This
>>> seems
>>>>>>>> to be the behavior when I attempt this.
>>>>>>>>
>>>>>>>> --
>>>>>>>> Dr. Robert Molt Jr.
>>>>>>>>
>>>>>>>>
>>>>>>>> _______________________________________________
>>>>>>>> AMBER mailing list
>>>>>>>> AMBER.ambermd.org
>>>>>>>> http://lists.ambermd.org/mailman/listinfo/amber
>>>>>>>>
>>>>>>> _______________________________________________
>>>>>>> AMBER mailing list
>>>>>>> AMBER.ambermd.org
>>>>>>> http://lists.ambermd.org/mailman/listinfo/amber
>>>>>> --
>>>>>> Dr. Robert Molt Jr.
>>>>>>
>>>>>> _______________________________________________
>>>>>> AMBER mailing list
>>>>>> AMBER.ambermd.org
>>>>>> http://lists.ambermd.org/mailman/listinfo/amber
>>>>>>
>>>>> _______________________________________________
>>>>> AMBER mailing list
>>>>> AMBER.ambermd.org
>>>>> http://lists.ambermd.org/mailman/listinfo/amber
>>>>>
>>> --
>>> Dr. Robert Molt Jr.
>>>
>>>
>>> _______________________________________________
>>> AMBER mailing list
>>> AMBER.ambermd.org
>>> http://lists.ambermd.org/mailman/listinfo/amber
>>>
>>
>>
>> _______________________________________________
>> AMBER mailing list
>> AMBER.ambermd.org
>> http://lists.ambermd.org/mailman/listinfo/amber
>
> --
> Dr. Robert Molt Jr.
>
> <bi6024269.pdf>
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber

_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Sat Apr 04 2020 - 15:00:02 PDT
Custom Search