I was hoping to ask a follow up question to one specific element of Dr.
Case's answer. Dr. Case wrote:
"The time scale for many such changes is on the microsecond to
millisecond time scale (or longer), and are hence not readily approached
by brute force simulations. (And, of course, current force fields may
not properly describe all of these alternate conformational basins.)"
I am confused by the parenthetical statement. Is there a particular
reason to believe that the quality of a force field varies by a
conformational basin? I would assume if one starts in basin A, the force
field should not be assumed to be more accurate there than in basin B?
Or is this just meant as a general "snipe" of force field limitations?
On 7/4/18 8:41 AM, David A Case wrote:
> On Wed, Jul 04, 2018, xmgign.126.com wrote:
>> And I have tried aMD and GaMD for several times and I can not get the
>> right protein conformation. The protein has significant conformational
>> change which has identified by X-ray. Does Amber has other enhenced
>> sampling method can simulate the protein allosteric effect?
> Expecting to see spontaneous allosteric conformational changes in a large
> protein via MD simulations may be unrealistic. The time scale for many such
> changes is on the microsecond to millisecond time scale (or longer), and are
> hence not readily approached by brute force simulations. (And, of course,
> current force fields may not properly describe all of these alternate
> conformational basins.)
>
> If you know a collective coordinate that would describe the change between
> the two conformers, you could try any of several enhanced sampling
> methods, from umbrella sampling to NFE (non-equilibrium free energy)
> methods. The nudged elastic band method is sometimes helpful in finding
> pathways between conformers. And you might learn something by starting a
> simulation in the target state that was "identified by X-ray".
>
> ...hope this helps.....dac
>
>
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--
Dr. Robert Molt Jr.
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Received on Wed Jul 04 2018 - 15:30:01 PDT
