AMBER Archive (2009)

Subject: Re: [AMBER] Gly -> Ala mutation

From: Adrian Roitberg (roitberg_at_qtp.ufl.edu)
Date: Mon Nov 09 2009 - 10:13:11 CST

Dear Manoj.

As Jason mentioned, there is no way to change it with mmpbsa.pl

you can write a pdb file, modify it by hand, read it into tleap to get a
new prmtop.

Changing your trajectory for those new coordinates requires some pretty
advanced scripting, but you need to do it by hand.

manoj singh wrote:
> Dear Prof. Simmerling,
>
> Thanks for the reply.
>
> The Gly I want to mutate has the plenty of space around it and its phi
> and psi are in most stable conformation.
>
> How exactly can I make this mutation using mm_pbsa.pl or any other method.
>
> I will be very thankful for your kind response.
>
> Manoj
>
>
> On Mon, Nov 9, 2009 at 10:13 AM, Carlos Simmerling
> <carlos.simmerling_at_gmail.com> wrote:
>> Leap uses the connectivity tree information in the library about bond
>> lengths, angles and default dihedral angles. making Gly into Ala is
>> straightforward in the sense that there is no ambiguity about where to put
>> the heavy atoms, but as Jason said it may well be that there is no room for
>> the Cbeta, and in reality the structure would relax to accommodate it.
>> instead you might get unreasonably high energies.
>>
>>
>> On Sun, Nov 8, 2009 at 3:16 PM, Jason Swails <jason.swails_at_gmail.com> wrote:
>>
>>> Hello,
>>>
>>> There are no scripts in the amber distribution that will do this mutation
>>> for MM-PBSA to use with alanine scanning. The only way to make this
>>> mutation is to create a PDB (you can use ambpdb), change GLY to ALA at the
>>> desired residue (deleting the hydrogens attached to CA) and loading the
>>> structure into leap. Leap will add the other atoms, but I don't know what
>>> algorithm it uses to do so.
>>>
>>> Good luck,
>>> Jason
>>>
>>> On Sun, Nov 8, 2009 at 2:14 PM, manoj singh <mks.amber_at_gmail.com> wrote:
>>>
>>>> Thanks for your reply.
>>>>
>>>> I understand the Gly can attain all PHI and PSI values, however other
>>> amino
>>>> acids can not. But, if the Gly is in "usual" conformation, is it possible
>>>> to
>>>> mutate it to Ala using any available technique/script in the process of
>>>> performing MM-PBSA.
>>>>
>>>> One more thing, when talking about electrostatic energy, one should not
>>>> forget desolvation energy.
>>>>
>>>> Manoj
>>>>
>>>>
>>>> On Sun, Nov 8, 2009 at 12:53 PM, Jason Swails <jason.swails_at_gmail.com
>>>>> wrote:
>>>>> Hello,
>>>>>
>>>>> You can write your own script/program to do the transformation. Soon
>>>> there
>>>>> will be a release of a new MM-PB(GB)SA script for amber that should be
>>>>> faster and more user-friendly (and should handle alanine-scanning more
>>>>> easily). However, even this new script does not handle Gly-Ala
>>> mutations
>>>>> since this is more complex than every other mutation. For every other
>>>>> residue, all that is needed to handle an alanine mutation is to remove
>>>>> extraneous atoms and readjust some bond lengths to match those in
>>>> alanine.
>>>>> Glycine is the only amino acid that has fewer atoms than alanine, so in
>>>>> order to perform that mutation, atoms would need to be added to the
>>>> system.
>>>>> This is non-trivial, because the question becomes "where do we add
>>> those
>>>>> extra atoms?" (Ala has more degrees of freedom than Gly)
>>>>>
>>>>> It may even be the case that in a specific conformation, an alanine
>>> would
>>>>> not even fit where there's a glycine, so you would get an unphysically
>>>> high
>>>>> penalty for mutating that residue. Thus, the short version, there is
>>> no
>>>>> clear-cut, systematic way to handle a Gly->Ala mutation, so it's not
>>>> done.
>>>>> Furthermore, alanine scanning is designed more to measure the
>>>> electrostatic
>>>>> (and perhaps VDW) effects that a particular sidechain has on the
>>> activity
>>>>> of
>>>>> a protein. Glycine (and proline, though Pro->Ala is an allowed
>>> mutation
>>>> in
>>>>> the upcoming version if not this one) more often serves a role in
>>>>> modulating
>>>>> the structure of a protein, so alanine scanning is often ill-suited to
>>>>> probing the importance of a Glycine in the first place.
>>>>>
>>>>> Hope this helps,
>>>>> Jason
>>>>>
>>>>> On Sun, Nov 8, 2009 at 12:25 PM, manoj singh <mks.amber_at_gmail.com>
>>>> wrote:
>>>>>> Hi all!
>>>>>>
>>>>>> The mm_pbsa.pl can't do Gly->Ala mutation. Is there any way to do
>>> this
>>>>>> mutation in trajectory.
>>>>>>
>>>>>> Sincerely,
>>>>>> _______________________________________________
>>>>>> AMBER mailing list
>>>>>> AMBER_at_ambermd.org
>>>>>> http://lists.ambermd.org/mailman/listinfo/amber
>>>>>>
>>>>>
>>>>>
>>>>> --
>>>>> ---------------------------------------
>>>>> Jason M. Swails
>>>>> Quantum Theory Project,
>>>>> University of Florida
>>>>> Ph.D. Graduate Student
>>>>> 352-392-4032
>>>>> _______________________________________________
>>>>> AMBER mailing list
>>>>> AMBER_at_ambermd.org
>>>>> http://lists.ambermd.org/mailman/listinfo/amber
>>>>>
>>>> _______________________________________________
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>>>>
>>>
>>>
>>> --
>>> ---------------------------------------
>>> Jason M. Swails
>>> Quantum Theory Project,
>>> University of Florida
>>> Ph.D. Graduate Student
>>> 352-392-4032
>>> _______________________________________________
>>> AMBER mailing list
>>> AMBER_at_ambermd.org
>>> http://lists.ambermd.org/mailman/listinfo/amber
>>>
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>
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-- 
                            Dr. Adrian E. Roitberg
                              Associate Professor
                             Quantum Theory Project
                            Department of Chemistry

                  Senior Editor. Journal of Physical Chemistry
                           American Chemical Society

University of Florida                         PHONE 352 392-6972
P.O. Box 118435                               FAX   352 392-8722
Gainesville, FL 32611-8435                    Email adrian_at_qtp.ufl.edu

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