Re: Selective accelerated MD in NAMD

From: Chitrak Gupta (chgupta_at_mix.wvu.edu)
Date: Sat Apr 07 2018 - 09:42:25 CDT

Hi Alex,

Thanks for the references, these were new to me. However, from what I
understand, all of these were done by home-built script (including the
Amber simulations in PNAS). As far as I know this is still not implemented
in the official release of Amber (and probably NAMD as well).

I have had similar issues where trying to use aMD/GaMD to model a very
loose binding wasn't fruitful because the acceleration ended up
destabilizing the complex itself. I will wait for others to comment on
whether there is a possible workaround to this.

Chitrak.

On Sat, Apr 7, 2018 at 8:00 AM, Alexander Adams <xadams_at_umich.edu> wrote:

> Hi Chitrak,
>
> I believe these are the relevant papers.
>
> Selective aMD in Desmond:
> Wereszczynski, J. & McCammon, J. A. Using selectively applied accelerated
> molecular dynamics to enhance free energy calculations. J. Chem. Theory
> Comput. 6, 3285–3292 (2010).
>
> Selective aMD in Amber:
> Doshi, U., McGowan, L. C., Ladani, S. T. & Hamelberg, D. Resolving the
> complex role of enzyme conformational dynamics in catalytic function. Proc.
> Natl. Acad. Sci. 109, 5699–5704 (2012).
>
> Review article of advances in aMD that directed me to these articles:
> Doshi, U. & Hamelberg, D. Towards fast, rigorous and efficient
> conformational sampling of biomolecules: Advances in accelerated molecular
> dynamics. Biochim. Biophys. Acta - Gen. Subj. 1850, 878–888 (2015).
>
> Hope this helps,
> Alex
>
> On Fri, Apr 6, 2018 at 6:42 PM, Chitrak Gupta <chgupta_at_mix.wvu.edu> wrote:
>
>> Hi Alexander,
>>
>> I was not aware that you could do accelerated MD on a part of your
>> system. Could you refer me to the relevant literature?
>>
>>
>> Chitrak.
>>
>> On Fri, Apr 6, 2018 at 4:36 PM, Alexander Adams <xadams_at_umich.edu> wrote:
>>
>>> Hi Eddi,
>>>
>>> Thank you for your response. I can choose just to boost the dihedrals of
>>> the system, though literature suggests that this is insufficient to observe
>>> the conformational changes associated with a transport event.
>>>
>>> Miao, Y., Nichols, S., Gasper, P., Metger, V. & McCammon, J. Activation
>>> and dynamic network of the M2 muscarinic receptor. Proc. Natl. Acad. Sci.
>>> U. S. A. 110, 10982–10987 (2013).
>>>
>>> Ke, M., Yuan, Y., Jiang, X., Yan, N. & Gong, H. Molecular determinants
>>> for the thermodynamic and functional divergence of uniporter GLUT1 and
>>> proton symporter XylE. PLoS Comput. Biol. 1–26 (2017).
>>>
>>> On Fri, Apr 6, 2018 at 4:23 PM, Eduard Schreiner <
>>> eduard.schreiner_at_gmail.com> wrote:
>>>
>>>> Can't you boost just the dihedrals of the protein?
>>>>
>>>> Eddi
>>>>
>>>> Alexander Adams <xadams_at_umich.edu> schrieb am Fr., 6. Apr. 2018, 21:12:
>>>>
>>>>> Hello all,
>>>>>
>>>>> I am performing a simulation of the transport protein XylE in membrane
>>>>> with the sugar xylose bound in the central pocket. I am using accelerated
>>>>> MD in order to access a conformation change on the nanosecond timescale.
>>>>> Unfortunately, the total potential boost results in the sugar unbinding
>>>>> from the central pocket central pocket and diffusing away from the protein.
>>>>> I know there is a form of aMD in Amber that allows for selective
>>>>> acceleration of just an enzyme, substrate, etc., and was wondering if an
>>>>> equivalent exists in NAMD.
>>>>>
>>>>> Thanks in advance!
>>>>> Alex Adams
>>>>>
>>>>
>>>
>>
>

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