[gmx-users] [gmx-user] MD simulation of protein-ligand complex

[Justin Lemkul]

On 12/24/19 6:46 PM, Quin K wrote:
> Thank you!
> Let's say I extracted several snapshots of protein and docked with the
> ligand separately and looked at the binding free-energy for each snapshot
> with the same ligand, provided global properties are fine, would this help
> in achieving stable complex during protein-ligand complex MD simulation?
>

Most complexes are stable on the time scale of conventional MD 
simulations. Additional sampling that we're discussing will perhaps help 
find a more optimal binding pose but I wouldn't expect any of this to 
make a complex "stable."

-Justin

>
> On Tue, Dec 24, 2019 at 7:33 PM Justin Lemkul <jalemkul at vt.edu> wrote:
>
>>
>> On 12/24/19 12:47 PM, Quin K wrote:
>>> Hi
>>> Which of the following is the correct method to prepare a protein for
>>> docking and then for protein-ligand complex MD simulation?
>>>
>>> 1. Do an MD simulation of protein for 100 ns and use the structure of
>>> protein at 100 ns to do the protein-ligand MD simulation.
>> There is no guarantee that the final snapshot is in any way
>> representative of the rest of the simulation, so this is basically an
>> arbitrary choice.
>>
>>> 2. Do an energy minimization of protein (like 5 ns) and use that
>> structure
>>> for MD simulation of protein-ligand complex.
>> Energy minimization is not dynamical, so there are no time units. This
>> is the more common approach (using an experimental structure) but is not
>> necessarily representative of the dominant structure that exists in
>> solution or that is receptive to ligand binding.
>>
>> The better approach is to choose a representative snapshot (or multiple)
>> from a long MD simulation with very careful analysis of local (binding
>> site) and global (overall structure) properties. Then you can make a
>> robust choice for a docking target (or multiple, depending on what you
>> find).
>>
>> -Justin
>>
>> --
>> ==================================================
>>
>> Justin A. Lemkul, Ph.D.
>> Assistant Professor
>> Office: 301 Fralin Hall
>> Lab: 303 Engel Hall
>>
>> Virginia Tech Department of Biochemistry
>> 340 West Campus Dr.
>> Blacksburg, VA 24061
>>
>> jalemkul at vt.edu | (540) 231-3129
>> http://www.thelemkullab.com
>>
>> ==================================================
>>
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-- 
==================================================

Justin A. Lemkul, Ph.D.
Assistant Professor
Office: 301 Fralin Hall
Lab: 303 Engel Hall

Virginia Tech Department of Biochemistry
340 West Campus Dr.
Blacksburg, VA 24061

jalemkul at vt.edu | (540) 231-3129
http://www.thelemkullab.com

==================================================